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PubMed2024

Prenatal diagnosis and molecular cytogenetic analysis of pure chromosome 10p15.3 microdeletion using chromosomal microarray analysis.

BACKGROUND: The literature contains exceedingly limited reports on chromosome 10p15.3 microdeletions. In the present study, two cases of fetuses with pure terminal 10p15.3 microdeletion syndrome in a Chinese population were examined, with the objective of enhancing understanding of the genotype-phenotype correlation associated with 10p15.3 microdeletions. METHODS: Two fetuses with chromosome 10p15.3 microdeletion were identified from a cohort of 5,258 cases undergoing amniocentesis. Karyotyping and chromosomal microarray analysis (CMA) was conducted to assess chromosomal abnormalities and detect copy number variations (CNVs) within the families, respectively. RESULTS: In Family 1, the fetus exhibited a 556.2-Kb deletion in the 10p15.3 region, encompassing OMIM genes such as DIP2C and ZMYND11, and presented with increased nuchal translucency on prenatal ultrasound examination. Parental CMA analysis revealed that the 10p15.3 microdeletion was inherited from the father, who displayed mild language impairment. In Family 2, a comparable 10p15.3 microdeletion was identified in a fetus presenting with asymmetric butterfly vertebrae at T10 and T12, along with mild scoliosis of the spine. Family 1 elected to terminate the pregnancy, while Family 2 chose to continue. At a follow-up conducted at one year and eight months, the child demonstrated delays in both speech and motor development. CONCLUSION: The present study is the first to report two cases of pure terminal chromosome 10p15.3 microdeletion syndrome in fetuses, offering valuable insights for the prenatal diagnosis of 10p15.3 microdeletion syndrome. Further, it is the first to describe mild clinical features, specifically limited to language impairment, in a patient with 10p15.3 microdeletion syndrome.

Female↗

PubMed2026

Prenatal SNP-array chromosomal microarray analysis in 3,549 pregnancies: indication-specific yields and clinical implications.

BACKGROUND: SNP-based chromosomal microarray analysis (CMA) is widely used in invasive prenatal diagnosis, yet real-world performance across contemporary referral pathways, especially in the NIPT era, remains incompletely characterized. METHODS: We retrospectively analyzed 3,549 prenatal invasive samples tested by SNP array, and evaluated diagnostic yield overall and by referral indication and ultrasound phenotype. RESULTS: In total, we identified 398 pathogenic or likely pathogenic (P/LP) variants across 386 fetuses, resulting in an overall diagnostic yield of 10.9% (386/3,549). These findings comprised 223 aneuploidies and 175 pathogenic CNVs. In contrast, variants of uncertain significance (VOUS) were detected in 12.0% (426/3,549) of cases. Diagnostic yields were heavily stratified by indication: yields peaked in NIPT high-risk referrals (38.9%) and were intermediate in ultrasound-based cases (~ 11%), but dropped significantly in the advanced maternal age (AMA; 4.2%) and serum screening (~ 5-6%) groups. Conversely, VOUS rates remained remarkably stable across all referral categories. Sub-analysis of ultrasound abnormalities revealed that multisystem anomalies conferred the highest risk (27.3%), driven predominantly by aneuploidies; among soft markers, increased nuchal translucency (NT) emerged as the strongest predictor of chromosomal pathology. CONCLUSIONS: In our cohort, SNP-array identified clinically actionable findings in 10.9% of cases. NIPT enriched diagnostic yields, particularly for aneuploidies, and NT thickness was strongly associated with pathogenic findings. These results support an indication-based approach to genomic testing, with NIPT as a triage tool for aneuploidy and CMA for high-risk populations, while improving VOUS counseling.

Humans↗

PubMed2025

Effective detection of 148 cases chromosomal mosaicism by karyotyping, chromosomal microarray analysis and QF-PCR in 32,967 prenatal diagnoses.

BACKGROUND: Detection of mosaicism has always been difficult in prenatal diagnosis, which is to assess the value of karyotyping combined with three different molecular genetic tests for prenatal diagnosis. Retrospective review of chromosomal mosaicism (CM) was conducted in 32,967 pregnant women from January 2015 to December 2022. METHODS: A total of 148 fetuses diagnosed with chromosomal mosaicism by karyotyping with copy number variant sequencing (CNV-seq)/ chromosomal microarray analysis (CMA) and quantitative fluorescent polymerase chain reaction (QF-PCR) were selected, and the results from three the methods were compared and further analyzed. The χ2 test for multiple group rates was for the 5 clinical prenatal diagnostic indication groups was used to do multiple comparison tests for statistical analysis. Inconsistent results between methods were identified and further analyzed. RESULTS: A total of 148 CM cases was detected (0.45%, 148/32967), of which karyotyping was detected in combination with CMA in 73 cases (73/85), with CNV-seq in 5 cases (5/11), and with QF-PCR in 35 cases (35/52) and the mosaic conformity rates of the three methods compared with karyotyping were 85.9% (CMA), 67.3% (QF-PCR), and 45.5% (CNV-seq), respectively. There were 49 cases of autosomal mosaicism (49/148, 33.1%) and 99 cases of sex CM (99/148, 66.9%). There were 9 cases of small supernumerary marker chromosome (sSMC)with CMA detection clarified the origin of chromosome fragments. The non-invasive prenatal testing (NIPT) group and the ultrasound abnormality group had the highest detection rates, accounting for 35.1% and 22.3%. CONCLUSIONS: In chromosomal mosaicism, there are inconsistent results between different detection methods. Therefore, karyotyping combined with CMA/CNV-seq and FISH methods significantly improves the detection rate of chromosomal mosaicism and also confirms experimental data in the literature, which is of great value for prenatal diagnosis.

Humans↗

PubMed2025

Detection of copy number variations by chromosomal microarray analysis in disorders of sex development of unexplained molecular etiology and association with clinical findings.

PURPOSE: Despite advances in genetic diagnostics, the molecular cause of a significant proportion of DSDs remains unknown. The aim of this study was to identify copy number variations (CNVs) using chromosomal microarray analysis (CMA) technology in DSD patients with previously undetected molecular genetic etiology and to investigate their phenotypic associations with these variations. METHODS: This study included DSD cases without chromosomal abnormalities and without any variants detected by sequence analysis methods, including whole-exome sequencing analysis. We evaluated variant pathogenicity according to the American College of Medical Genetics and Genomics guidelines and recorded the phenotypic findings of the cases. All pathogenic variants were subjected to segregation analysis. RESULTS: Of the 20 patients included in the study, 16 (80%) were classified as 46,XY DSD and 4 (20%) as 46,XX DSD. Initial clinical diagnoses in this 46,XX DSD group included gonadal dysgenesis in two patients (50%) and androgen excess in the remaining two (50%). Among the 46,XY DSD patients, five patients (31.25%) were presumed to be androgen insensitive, nine (56.25%) were diagnosed with defects in androgen biosynthesis, and two (12.5%) had gonadal dysgenesis. CMA detected 38 CNVs in 16 patients (80%), comprising 12 deletions (31.6%) and 26 duplications (68.4%). Three pathogenic CNVs were detected in 3 patients (15%), whereas 27 variants of uncertain significance were identified in 13 patients (65%). CONCLUSION: In selected cases, the diagnostic approach should incorporate CMA to elucidate the molecular etiology of DSD. Furthermore, CMA may prove to be an invaluable tool in the search for new genes responsible for DSD.

Humans↗

PubMed2005

Evolution of prenatal genetics: from point mutation testing to chromosomal microarray analysis.

Molecular genetic testing involves DNA analysis using various methods for the purpose of diagnosing genetic disorders. In the prenatal DNA diagnostic setting, fetal DNA is usually tested for a specific single-gene disorder for which the fetal risk is 25% or more. In contrast, cytogenetic testing is often used to detect fetal chromosomal abnormalities in cases that involve a wider range of indications. Classic cytogenetic and DNA-based testing methods provide a range of aberrations detected with different levels of genomic resolution. More recently developed molecular cytogenetic methods provide powerful tools to bridge the technical divide between these related areas. One such hybrid method is microarray-based comparative genomic hybridization. Chromosomal microarray analysis has been applied to clinical testing for unbalanced gains or losses of genomic regions associated with genetic disorders. This technology is poised to have a substantial impact on clinical genetics, including prenatal genetic testing.

Chromosome Aberrations↗

PubMed2004

MACAT--microarray chromosome analysis tool.

UNLABELLED: By linking differential gene expression to the chromosomal localization of genes, one can investigate microarray data for characteristic patterns of expression phenomena involving sizeable parts of specific chromosomes. We have implemented a statistical approach for identifying significantly differentially expressed chromosome regions. We demonstrate the applicability of the approach on a publicly available data set on acute lymphocytic leukemia. AVAILABILITY: The R-package MACAT can be obtained from http://www.compdiag.molgen.mpg.de/software/macat.shtml SUPPLEMENTARY INFORMATION: http://www.compdiag.molgen.mpg.de/software/macat.shtml.

Algorithms↗

PubMed2004

DNA microarray analysis of chromosomal susceptibility regions to identify candidate genes for allergic disease: a pilot study.

OBJECTIVE: To examine whether DNA microarray analysis of chromosomal susceptibility regions for allergy can help to identify candidate genes. MATERIAL AND METHODS: Nasal biopsies were obtained from 23 patients with allergic rhinitis and 12 healthy controls. RNA was extracted from the biopsies and pooled into three patient and three control pools. These were then analysed in duplicate with DNA microarrays containing 12626 genes. Candidate genes were further examined in nasal biopsies (real-time polymerase chain reaction) and blood samples (single nucleotide polymorphisms) from other patients with allergic rhinitis and from controls. RESULTS: A total of 37 differentially expressed genes were identified according to criteria involving both the size and consistency of the gene expression levels. The chromosomal location of these genes was compared with the chromosomal susceptibility regions for allergic disease. Using a statistical method, five genes were identified in these regions, including serine protease inhibitor, Kazal type, 5 (SPINK5) and HLA-DRB2. The relevance of these genes was examined in other patients with allergic rhinitis and in controls; none of the genes were differentially expressed in nasal biopsies. Moreover, no association between allergic rhinitis and SPINK5 polymorphisms was found, at either the genotype or haplotype level. CONCLUSIONS: DNA microarray analysis of chromosomal susceptibility regions did not lead to identification of candidate genes that could be validated in a new material. However, because gene polymorphisms may cause differential gene expression, further studies, including validation data, are needed to examine this approach.

Adolescent↗

PubMed2006

Evidence for involvement of TRE-2 (USP6) oncogene, low-copy repeat and acrocentric heterochromatin in two families with chromosomal translocations.

We report clinical findings and molecular cytogenetic analyses for two patients with translocations [t(14;17)(p12;p12) and t(15;17)(p12;p13.2)], in which the chromosome 17 breakpoints map at a large low-copy repeat (LCR) and a breakage-prone TRE-2 (USP6) oncogene, respectively. In family 1, a 6-year-old girl and her 5-year-old brother were diagnosed with mental retardation, short stature, dysmorphic features, and Charcot-Marie-Tooth disease type 1A (CMT1A). G-banding chromosome analysis showed a der(14)t(14;17)(p12;p12) in both siblings, inherited from their father, a carrier of the balanced translocation. Chromosome microarray and FISH analyses revealed that the PMP22 gene was duplicated. The chromosome 17 breakpoint was mapped within an approximately 383 kb LCR17pA that is known to also be the site of several breakpoints of different chromosome aberrations including the evolutionary translocation t(4;19) in Gorilla gorilla. In family two, a patient with developmental delay, subtle dysmorphic features, ventricular enlargement with decreased periventricular white matter, mild findings of bilateral perisylvian polymicrogyria and a very small anterior commissure, a cryptic duplication including the Miller-Dieker syndrome region was identified by chromosome microarray analysis. The chromosome 17 breakpoint was mapped by FISH at the TRE-2 oncogene. Both partner chromosome breakpoints were mapped on the short arm acrocentric heterochromatin within or distal to the rRNA cluster, distal to the region commonly rearranged in Robertsonian translocations. We propose that TRE-2 together with LCR17pA, located approximately 10 Mb apart, also generated the evolutionary gorilla translocation t(4;19). Our results support previous observations that the USP6 oncogene, LCRs, and repetitive DNA sequences play a significant role in the origin of constitutional chromosome aberrations and primate genome evolution.

Charcot-Marie-Tooth Disease↗

PubMed2026

Evaluation of the efficacy of optical genome mapping in prenatal diagnosis: a retrospective cohort study.

BACKGROUND: Optical genome mapping (OGM) is an emerging cytogenetic method for concurrently detecting structural variants (SVs) and copy number variants (CNVs). However, its clinical application in prenatal diagnosis remains underexplored. METHODS: This study retrospectively evaluated the clinical validity of OGM in prenatal diagnosis by comparing with two routine genetic testing methods: karyotyping and chromosomal microarray analysis (CMA). Both positive and negative cases detected by routine genetic methods were enrolled to evaluate the technical concordance of OGM and its capability to improve diagnostic rate in negative cases. The exclusion criteria were balanced centromeric translocations, mosaic cases with cellular fractions < 20%, and loss of heterozygosity (LOH) < 25 Mb. All samples subjected to OGM testing were anonymized and analyzed blindly. The results from OGM were compared with those from routine genetic testing, and statistical analyses were performed to assess technical concordance and diagnostic rate. RESULTS: Of 217 samples (166 positive samples and 51 negative samples for routine genetic testing), all were successfully tested with OGM, including 2 umbilical cord blood samples, 4 chorionic villi samples, and 211 cultured amniotic fluid samples. Of the 207 reportable chromosomal aberrations from 166 positive samples, the blinded concordance between OGM and CMA, karyotyping, and combination of karyotyping plus CMA was 97.81%, 96.36%, and 97.10%, respectively. OGM missed six aberrations initially, including one LOH, two marker chromosomes, and three microdeletions. However, after reanalysis, its concordance improved to 100% with CMA and 99.03% with karyotyping plus CMA. OGM also diagnosed one additional case of a 3-kb deletion in 51 negative samples, improving the diagnostic rate by 1.96%. Moreover, OGM reclassified the pathogenicity of two microdeletions from pathogenic to uncertain significance in 2 positive cases. Furthermore, OGM clarified the diagnosis suspected by routine genetic testing and improved diagnostic accuracy in some cases. CONCLUSION: As far as we know, this is the largest retrospective study on OGM in prenatal diagnosis, and it includes a broad range of sample types. The results showed that OGM exhibits high concordance among the tested methods and increases the diagnostic rate. Thus, OGM has the potential to become a first-line technique for prenatal diagnosis in the future.

Humans↗

PubMed2026

Three-Year Experience of Cytogenetic and Molecular Genetic Evaluation in Patients With Disorders of Sex Development at a Tertiary Care Centre in Eastern India.

OBJECTIVES: Disorders of sex development (DSD) include a range of conditions in which chromosomal, gonadal, or anatomical sex deviates from the typical developmental pathway. The diagnostic approach to DSD has shifted from karyotyping to molecular genetic tools. This study evaluated the clinical presentation, cytogenetic spectrum, and diagnostic utility of conventional and advanced molecular genetic investigations in patients with suspected DSD managed at a tertiary care facility in Eastern India over a three-year period. METHODS: A retrospective observational study was conducted at the Genetics Laboratory of a tertiary care teaching hospital in Eastern India. Consecutive patients with clinically suspected DSD referred between January 2022 and December 2024 were included. Demographic and clinical data were obtained from referral records, and peripheral blood samples were analysed using standard G-banded karyotyping according to the International System for Human Cytogenomic Nomenclature (ISCN 2020). Fluorescence in situ hybridisation (FISH), chromosomal microarray analysis (CMA), and whole-genome sequencing (WGS) were selectively performed in cases with inconclusive cytogenetic findings, suspected structural chromosomal abnormalities, or complex phenotypes. RESULTS: A total of 98 suspected DSD cases were evaluated during the study period. The most frequent chromosomal constitution was 46,XY DSD (37, 37.8%), followed by 46,XX DSD (30, 30.6%) and sex chromosome DSD (21, 21.4%). Culture failure occurred in 10 (10.2%) samples. Advanced genetic techniques, including FISH, CMA, and WGS, improved diagnostic clarification in selected complex cases. CONCLUSION: This experience highlights the importance of integrating contemporary high-resolution technologies with conventional cytogenetics to enhance the assessment, counselling, and treatment of individuals with DSD.

chromosomal analysis↗

PubMedDate not supplied

Development and validation of a CGH microarray for clinical cytogenetic diagnosis.

PURPOSE: We developed a microarray for clinical diagnosis of chromosomal disorders using large insert genomic DNA clones as targets for comparative genomic hybridization (CGH). METHODS: The array contains 362 FISH-verified clones that span genomic regions implicated in over 40 known human genomic disorders and representative subtelomeric clones for each of the 41 clinically relevant human chromosome telomeres. Three or four clones from almost all deletion or duplication genomic regions and three or more clones for each subtelomeric region were included. We tested chromosome microarray analysis (CMA) in a masked fashion by examining genomic DNA from 25 patients who were previously ascertained in a genetic clinic and studied by conventional cytogenetics. A novel software package implemented in the R statistical programming language was developed for normalization, visualization, and inference. RESULTS: The CMA results were entirely consistent with previous cytogenetic and FISH findings. For clone by clone analysis, the sensitivity was estimated to be 96.7% and the specificity was 99.1%. Major advantages of this selected human genome array include the following: interrogation of clinically relevant genomic regions, the ability to test for a wide range of duplication and deletion syndromes in a single analysis, the ability to detect duplications that would likely be undetected by metaphase FISH, and ease of confirmation of suspected genomic changes by conventional FISH testing currently available in the cytogenetics laboratory. CONCLUSION: The array is an attractive alternative to telomere FISH and locus-specific FISH, but it does not include uniform coverage across the arms of each chromosome and is not intended to substitute for a standard karyotype. Limitations of CMA include the inability to detect both balanced chromosome changes and low levels of mosaicism.

Chromosome Aberrations↗

PubMed2026

Prenatal exome sequencing of fetuses with central nervous system anomalies based on prenatal ultrasound and magnetic resonance imaging diagnosis: A retrospective cohort study with a systematic review and meta-analysis.

INTRODUCTION: Fetal central nervous system (CNS) abnormalities have diverse etiologies, with genetic factors as a major contributor. Prenatal exome sequencing (ES) is a powerful tool for precise molecular diagnosis of CNS anomalies, but its diagnostic yield varies among studies. This study aimed to evaluate the additional diagnostic yield of prenatal ES compared with chromosomal microarray analysis (CMA) in fetuses with CNS anomalies detected by prenatal imaging. MATERIAL AND METHODS: We collected ES results from fetuses diagnosed with CNS anomalies by prenatal imaging (2019-2024) who had negative results. Subgroup analyses assessed phenotype-specific ES diagnostic yield for associated genes and variants. A systematic review and meta-analysis incorporating our data and published studies further explored the association between phenotype and diagnostic yield. RESULTS: In the cohort study of 219 cases, ES identified pathogenic/likely pathogenic single nucleotide variations in 36 cases (16%). The highest diagnostic yield of ES was in cases with multisystem malformations (25%, 14/55), followed by multiple CNS anomalies (15%, 2/13) and isolated CNS anomalies (13%, 20/151). The most commonly identified isolated CNS anomaly was agenesis of the corpus callosum (31%, 5/16). Neural tube defects with urogenital anomalies were associated with a positive ES finding in 57% (4/7) of cases. The meta-analysis of 989 cases from 22 studies showed a pooled diagnostic yield of ES of 27% (95% CI, 21%-34%). The highest diagnostic yield of ES was in cases of corpus callosum anomalies with facial abnormalities (75%, 8/11) and neural tube defects with urogenital malformations (80%, 12/15). The diagnostic yield of ES for three or more CNS abnormalities was 43% (95% CI, 31%-58%), significantly higher than that for only two abnormalities (10%, 95% CI, 4%-18%). No significant difference in diagnostic yield was found between cases identified by prenatal MRI combined with ultrasound (27%, 95% CI, 20%-36%) and those identified by ultrasound alone (25%, 95% CI, 17%-35%). CONCLUSIONS: ES provided a significantly higher diagnostic yield than CMA for fetal CNS abnormalities, with diagnostic yields varying by phenotype. The systematic review and meta-analysis confirmed that the complexity and combination of malformations are key factors associated with differences in ES diagnostic yield.

Humans↗

PubMed2026

[Pathogenicity analysis and prenatal genetic counseling for five Chinese pedigrees harboring a hemizygous c.-32C>G variant of FGF13 gene].

OBJECTIVE: To explore the pathogenicity and prenatal counseling strategies for five Chinese pedigrees harboring a hemizygous c.-32C>G (NM_001139500.2) variant of fibroblast growth factor 13 (FGF13) gene. METHODS: Five Chinese pedigrees found to carry a hemizygous c.-32C>G variant of the FGF13 gene at the Prenatal Diagnosis Center of Henan Provincial People's Hospital between January 2024 and January 2025 were selected as study subjects. The pedigrees had undergone prenatal diagnosis for a family history of genetic disorders, abnormal fetal ultrasound findings, or advanced maternal age. A retrospective analysis was carried out, wherein clinical data for all members of the pedigrees were obtained through the medical records system and outpatient visit system. Peripheral blood samples were collected from all pedigree members, and amniotic fluid samples were obtained from the probands. Following extraction of genomic DNA, prenatal diagnosis was performed using chromosomal microarray analysis (CMA) and trio whole-exome sequencing (trio-WES). Sanger sequencing was used to determine the carrier status for the candidate variant, and Mini-Mental State Examination (MMSE) was used to assess the cognitive function of hemizygous individuals carrying the FGF13 gene c.-32C>G variant. Pathogenicity of candidate variant was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-171). RESULTS: CMA and trio-WES revealed no pathogenic variants in all probands, whilst trio-WES and Sanger sequencing had identified 11 male individuals carrying a hemizygous c.-32C>G variant of the FGF13 gene from the five pedigrees, which included six adult males, a young boy, and four fetuses. One fetus had undergone termination of pregnancy due to hydrocephalus, one was born pre-term at 34+1 weeks of gestation owing to maternal hypertension, and other two were delivered at full term. Follow-up of the survived males revealed no phenotypic manifestations related to language or intellectual impairment. Among these, three adult males underwent the MMSE assessment, all of whom showed normal cognitive function. Search of the gnomAD database suggested the carrier frequency of FGF13 c.-32C>G variant in the East Asian population to be 0.125%, with 11 hemizygous males documented. Three male patients harboring the variant showed severe intellectual disability. Both in vitro and in vivo studies suggested that it could reduce the translation levels of FGF13 protein. Based on the ACMG guidelines, it was classified as variant of uncertain significance (BS4+PS3_Supporting). CONCLUSION: There is insufficient evidence to classify the FGF13 c.-32C>G as a pathogenic variant in clinical practice, and its presence should not be considered an indication for pregnancy termination due to major birth defects.

Adult↗

PubMed2026

Genomic risk profiling in advanced maternal age: a Tamil Nadu prenatal study.

BACKGROUND: Advanced maternal age (AMA; > = 35 years) is associated with increased fetal chromosomal risk and is an important indication for invasive prenatal diagnosis. This study evaluates karyotyping and chromosomal microarray analysis (CMA) findings among AMA pregnancies in Tamil Nadu, India. METHODS: In this prospective observational study, 2,200 pregnant women aged ≥35 years who underwent amniocentesis between July 2020 and June 2021 were enrolled. Conventional karyotyping was performed in all cases. CMA was performed as a reflex or complementary test when predefined clinical or cytogenetic criteria were present, including ultrasound abnormalities, high-risk screening/NIPT results, abnormal or uncertain karyotype findings, prior adverse pregnancy history suggestive of genetic etiology, parental chromosomal abnormalities, or patient request after counseling. RESULTS: Numerical chromosomal abnormalities were detected in 76/2200 cases (3.5%), and structural abnormalities were detected in 9/2200 cases (0.4%). The total abnormal cytogenetic yield was therefore 85/2200 cases (3.9%) when numerical and structural abnormalities were considered together. Age-stratified analysis showed an increasing trend in chromosomal abnormalities with advancing maternal age, reaching 10.4% in women aged > = 43 years. Cases with additional clinical indications showed higher abnormality rates than simple AMA. CMA was performed in selected cases and contributed to characterization of clinically relevant genomic abnormalities, supporting its role in indicated high-risk AMA pregnancies. CONCLUSION: The Tamil Nadu cohort provides regional evidence on age-stratified cytogenetic risk in AMA pregnancies and supports the use of clearly defined criteria for integrating CMA with conventional karyotyping in prenatal diagnosis.

India↗

PubMed2005

Tiling microarray analysis of rice chromosome 10 to identify the transcriptome and relate its expression to chromosomal architecture.

BACKGROUND: Sequencing and annotation of the genome of rice (Oryza sativa) have generated gene models in numbers that top all other fully sequenced species, with many lacking recognizable sequence homology to known genes. Experimental evaluation of these gene models and identification of new models will facilitate rice genome annotation and the application of this knowledge to other more complex cereal genomes. RESULTS: We report here an analysis of the chromosome 10 transcriptome of the two major rice subspecies, japonica and indica, using oligonucleotide tiling microarrays. This analysis detected expression of approximately three-quarters of the gene models without previous experimental evidence in both subspecies. Cloning and sequence analysis of the previously unsupported models suggests that the predicted gene structure of nearly half of those models needs improvement. Coupled with comparative gene model mapping, the tiling microarray analysis identified 549 new models for the japonica chromosome, representing an 18% increase in the annotated protein-coding capacity. Furthermore, an asymmetric distribution of genome elements along the chromosome was found that coincides with the cytological definition of the heterochromatin and euchromatin domains. The heterochromatin domain appears to associate with distinct chromosome level transcriptional activities under normal and stress conditions. CONCLUSION: These results demonstrated the utility of genome tiling microarray in evaluating annotated rice gene models and in identifying novel transcriptional units. The tiling microarray sanalysis further revealed a chromosome-wide transcription pattern that suggests a role for transposable element-enriched heterochromatin in shaping global transcription in response to environmental changes in rice.

Chromosomes, Plant↗

PubMed2026

A case report of Xp21 contiguous gene deletion syndrome with adrenal crisis and sensorineural hearing loss: clinical highlights and management pitfalls.

OBJECTIVES: To report a rare association of Xp21 contiguous gene deletion syndrome (CGDS) featuring sensorineural hearing loss (SNHL), and to discuss the diagnostic and therapeutic challenges. CASE PRESENTATION: A male infant presented with a salt-wasting adrenal crisis consistent with X-linked adrenal hypoplasia congenita. His follow-up clinical course during childhood revealed global developmental delay and SNHL, the latter of which has been under-reported in the literature for this condition. At five years of age, the development of progressive proximal muscle weakness and markedly elevated creatine phosphokinase levels led to a diagnosis of Duchenne muscular dystrophy (DMD). The patient also exhibited pseudohypertriglyceridemia and elevated urinary glycerol, consistent with glycerol kinase deficiency. While initial exome sequencing failed to detect the genetic abnormality, subsequent chromosomal microarray analysis identified an Xp21 CGDS involving NR0B1, IL1RAPL1, DMD, and GK. Treatment of adrenal insufficiency with fludrocortisone and hydrocortisone was complicated by the higher steroid doses required for the management of DMD, resulting in exogenous Cushing syndrome and associated complications. CONCLUSIONS: This case highlights the necessity of evaluating for Xp21 CGDS in patients presenting with adrenal crisis and emphasizes the importance of multidisciplinary management to optimize outcomes in this complex pediatric endocrine disorder.

Humans↗

PubMed2026

[Aggressive B-cell lymphomas with MYC gene cluster amplification: a clinicopathological analysis of eight cases].

Objective: To investigate the clinicopathological characteristics, molecular genetics, treatments and prognosis of aggressive B-cell lymphomas (ABCL) with MYC gene cluster amplification. Methods: Eight cases of ABCL with MYC gene cluster amplification were collected, including 6 cases from the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China and 2 consultation cases from outside hospitals. The histomorphology, immunohistochemical profiles, and molecular genetic characteristics were analyzed. Clinical follow-up and literature review were also conducted. Results: Among the eight patients, six were male and two were female, with an age 71.5 (61.7, 74.2) years. All six in-house patients presented with abdominal pain at onset, without B symptoms. Most cases were classified as Ann Arbor stage Ⅲ-Ⅳ. Extranodal involvement occurred in 5 of the 6 in-house cases, primarily affecting the gastrointestinal tract (4/5). All initial bone marrow biopsies showed no evidence of lymphoma. One patient had a history of immunosuppression following renal transplantation. Two cases exhibited diffuse large B-cell lymphoma (DLBCL) morphology. The other six showed high-grade features, while three of them showed Burkitt lymphoma-like morphology. Except for one case of blastoid variant mantle cell lymphoma, the remaining six cases (6/7) displayed a germinal center B-cell phenotype. None of the in-house cases harbored bcl-2 or bcl-6 rearrangements as shown by fluorescence in situ hybridization. 11q alterations were identified in all but one consultation case, including gain/loss type in five cases and 11q gain in two. 11q telomere loss of heterozygosity by chromosomal microarray analysis was not detected in one of the two cases with 11q gain that was subject to the test. The duration of follow-up ranged from 5.9 to 55.5 months, with 5 patients alive at the end of the study. Conclusions: ABCL with MYC gene cluster amplification often presents high-grade morphology and gastrointestinal involvement, which strongly suggests the alteration of 11q. It seems to have a favorable prognosis.

Humans↗

PubMed2006

Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males.

PURPOSE: Mutations in the MECP2 gene are associated with Rett syndrome, an X-linked mental retardation disorder in females. Mutations also cause variable neurodevelopmental phenotypes in rare affected males. Recent clinical testing for MECP2 gene rearrangements revealed that entire MECP2 gene duplication occurs in some males manifesting a progressive neurodevelopmental syndrome. METHODS: Clinical testing through quantitative DNA methods and chromosomal microarray analysis in our laboratories identified seven male patients with increased MECP2 gene copy number. RESULTS: Duplication of the entire MECP2 gene was found in six patients, and MECP2 triplication was found in one patient with the most severe phenotype. The Xq28 duplications observed in these males are unique and vary in size from approximately 200 kb to 2.2 Mb. Three of the mothers who were tested were asymptomatic duplication carriers with skewed X-inactivation. In silico analysis of the Xq28 flanking region showed numerous low-copy repeats with potential roles in recombination. CONCLUSIONS: These collective data suggest that increased MECP2 gene copy number is mainly responsible for the neurodevelopmental phenotypes in these males. These findings underscore the allelic and phenotypic heterogeneity associated with the MECP2 gene and highlight the value of molecular analysis for patient diagnosis, family members at risk, and genetic counseling.

Adolescent↗