Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Microdeletion”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources
PubMed2004

Prevalence of chromosomal abnormalities in 2078 infertile couples referred for assisted reproductive techniques.

BACKGROUND: This study analyses the prevalence of karyotype changes and Yq11 microdeletions among couples referred for assisted reproduction techniques. METHODS: Prior to receiving either IVF or ICSI treatment, each partner of 2078 infertile couples was screened for karyotype changes by GTG-banding technique on peripheral lymphocytes. No subject presented with obvious phenotype of chromosomal rearrangement. All the oligo/azoospermic men with normal karyotype were further investigated by PCR for Yq11 microdeletions. RESULTS: Eighty-two out of 2078 couples (3.95%) had one partner carrying a chromosomal change, and 10 out of 202 (4.95%) men showed Yq11 microdeletions. The chromosomal rearrangements were 44 (2.1%) translocations, 23 (1.1%) gonosomal mosaics, six (0.3%) 47,XXY, five (0.24%) marker chromosomes, three (0.14%) inversions and one (0.05%) duplication. Frequency of anomalies in men and women were similar: 42 and 40 cases respectively. CONCLUSIONS: Partners of infertile couples requiring IVF or ICSI treatment appear to be affected by higher frequency of chromosomal rearrangements than the general population. Categories with greater risk were represented by men with sperm cell count <20 x 10(6) sperm/ml, and women with history of pregnancy loss.

Adult↗
PubMed2003

No AZF deletion in 160 patients with testicular germ cell neoplasia.

Testicular germ cell cancer is aetiologically linked to genital malformations and male infertility and is most probably caused by a disruption of embryonic programming and gonadal development during fetal life. In some cases, germ cell neoplasia is associated with a relative reduction of Y chromosomal material (e.g. 45,X/46,XY) or other abnormalities of the Y chromosome. The euchromatic long arm of the human Y chromosome (Yq11) contains three azoospermia factors (AZFa, AZFb, AZFc) functionally important in human spermatogenesis. Microdeletions encompassing one of these three AZF loci result in the deletion of multiple genes normally expressed in testis tissue and are associated with spermatogenic failure. The aim of our study was to investigate whether AZF microdeletions, in addition to causing infertility, predispose also to germ cell neoplasia, since subjects with poor spermatogenesis have an increased risk of testicular cancer. We screened for putative deletions of AZF loci on the Y chromosome in DNA isolated from white blood cells of 160 Danish patients with testicular germ cell neoplasia. Interestingly, although AZF microdeletions are found frequently in patients with idiopathic infertility, in all cases studied of testicular germ cell cancer the Yq region was found to be intact. We conclude that the molecular aetiology of testicular germ cell neoplasia of the young adult type most likely does not involve the same pathways as male infertility caused by AZF deletions. Malignant transformation of germ cells is thus caused by the dysfunction of some other genes that still need to be identified.

Adult↗
PubMed2003

22q11 deletion: a multisystem disorder requiring multidisciplinary input.

AIM: To draw up recommendations for the investigation and management of children with a microdeletion of chromosome 22q11. METHODS: A retrospective review of case notes from patients with a chromosome 22q11 microdeletion identified by cytogenetics laboratories of the south and west of Britain over a four year period. RESULTS: A total of 210 cases were identified. Age at diagnosis was 0-1 years (34%), 1-4 (17%), 5-17 (35%), and 18 years or more (13%). School age children were less likely to be investigated than infants: echocardiography in school age 86% v in infancy 97%, serum calcium 66% v 89%, renal ultrasound scan 38% v 42%, lymphocyte count 26% v 68%, parental karyotype 78% v 88%. The yield of investigations remained high throughout all age groups with 42% of school age children shown to have hypocalcaemia and 25% abnormal findings on renal ultrasound. CONCLUSIONS: 22q11 microdeletion is a multisystem disorder requiring a set of core investigations at diagnosis. We recommend an echocardiogram, renal ultrasound scan, lymphocyte count and function, serum calcium, and parental karyotype as a minimum. Genetic counselling and community paediatric input is helpful for most families.

Adolescent↗
PubMed2003

Common arterial trunk in the fetus: characteristics, associations, and outcome in a multicentre series of 23 cases.

OBJECTIVE: To assess the accuracy of prenatal diagnosis, the incidence of extracardiac and chromosomal anomalies, and the perinatal outcome in a population of fetuses with common arterial trunk (CAT). DESIGN: Observational study of 23 fetuses from three referral centres with a confirmed diagnosis of CAT. All underwent fetal echocardiography, detailed anatomical scanning, and karyotyping. In 19 cases, FISH analysis was done to detect 22q11 microdeletion. The following variables were evaluated: gestational age at diagnosis, anatomical variants of the CAT, presence of extracardiac and chromosomal anomalies, pregnancy, and fetal-neonatal outcome. Necropsy reports and postnatal files were available for confirmation of the prenatal diagnosis in all cases. RESULTS: The prenatal diagnosis proved correct in 23 of 24 cases, the last being pulmonary atresia with ventricular septal defect (PAVSD). A second cardiovascular anomaly was present in eight cases (34.8%); extracardiac anomalies were found in 10 (43.4%). FISH analysis showed 22q11 microdeletion in six of 19 cases (31.6%). Outcomes were as follows: eight terminations of pregnancy (34.8%), two intrauterine deaths (8.7%), five postnatal deaths (before or after surgery) (21.7%); the remaining eight neonates (34.8%) are alive and thriving after surgery (six) or awaiting surgery (two). CONCLUSIONS: CAT can be reliably diagnosed and characterised in prenatal life, although differentiation from PAVSD may be challenging. The association with chromosomal anomalies is consistent (8.7%), but there is a higher risk of 22q11 microdeletion (31.6%), in agreement with postnatal studies. The relatively poor survival rate (34.8%) reflects the high rate of terminations and the unfavourable cardiac anatomy in some cases.

Aorta, Thoracic↗
PubMed2002

Prospective screening for subtelomeric rearrangements in children with mental retardation of unknown aetiology: the Amsterdam experience.

OBJECTIVE: The frequency of subtelomeric rearrangements in patients with unexplained mental retardation (MR) is uncertain, as most studies have been retrospective and case retrieval may have been biased towards cases more likely to have a chromosome anomaly. To ascertain the frequency of cytogenetic anomalies, including subtelomeric rearrangements, we prospectively screened a consecutive cohort of cases with unexplained MR in an academic tertiary centre. METHODS: Inclusion criteria were: age <18 years at referral, IQ<85, no aetiological diagnosis after complete examination, which included karyotyping with high resolution banding (HRB). RESULTS: In 266 karyotyped children, anomalies were detected in 20 (7.5%, seven numerical, 13 structural); 39 cases were analysed by FISH for specific interstitial microdeletions, and anomalies were found in nine (23%). FISH analyses for subtelomeric microdeletions were performed in 184 children (44% moderate-profound MR, 51% familial MR), and one rearrangement (0.5%) was identified in a non-familial MR female with mild MR (de novo deletion 12q24.33-qter). The number of probable polymorphisms was considerable: 2qter (n=7), Xpter (n=3), and Ypter (n=1). A significantly higher total number of malformations and minor anomalies was present in the cytogenetic anomaly group compared to the group without cytogenetic anomalies. CONCLUSIONS: The total frequency of cytogenetic anomalies in this prospective study was high (1:10), but the frequency of subtelomeric rearrangements was low. The most likely explanations are the high quality of HRB cytogenetic studies and the lack of clinical selection bias. Conventional cytogenetic analyses, combined with targeted microdeletion testing, remain the single most effective way of additional investigation in mentally retarded children, also in a tertiary centre.

Adolescent↗
PubMed2006

Epigenetic inactivation of the HOXA gene cluster in breast cancer.

Using an integrated approach of epigenomic scanning and gene expression profiling, we found aberrant methylation and epigenetic silencing of a small neighborhood of contiguous genes-the HOXA gene cluster in human breast cancer. The observed transcriptional repression was localized to approximately 100 kb of the HOXA gene cluster and did not extend to genes located upstream or downstream of the cluster. Bisulfite sequencing, chromatin immunoprecipitation, and quantitative reverse transcription-PCR analysis confirmed that the loss of expression of the HOXA gene cluster in human breast cancer is closely linked to aberrant DNA methylation and loss of permissive histone modifications in the region. Pharmacologic manipulations showed the importance of these aberrant epigenetic changes in gene silencing and support the hypothesis that aberrant DNA methylation is dominant to histone hypoacetylation. Overall, these data suggest that inactivation of the HOXA gene cluster in breast cancer may represent a new type of genomic lesion-epigenetic microdeletion. We predict that epigenetic microdeletions are common in human cancer and that they functionally resemble genetic microdeletions but are defined by epigenetic inactivation and transcriptional silencing of a relatively small set of contiguous genes along a chromosome, and that this type of genomic lesion is metastable and reversible in a classic epigenetic fashion.

Breast Neoplasms↗
PubMed2006

Analysis and visualization of chromosomal abnormalities in SNP data with SNPscan.

BACKGROUND: A variety of diseases are caused by chromosomal abnormalities such as aneuploidies (having an abnormal number of chromosomes), microdeletions, microduplications, and uniparental disomy. High density single nucleotide polymorphism (SNP) microarrays provide information on chromosomal copy number changes, as well as genotype (heterozygosity and homozygosity). SNP array studies generate multiple types of data for each SNP site, some with more than 100,000 SNPs represented on each array. The identification of different classes of anomalies within SNP data has been challenging. RESULTS: We have developed SNPscan, a web-accessible tool to analyze and visualize high density SNP data. It enables researchers (1) to visually and quantitatively assess the quality of user-generated SNP data relative to a benchmark data set derived from a control population, (2) to display SNP intensity and allelic call data in order to detect chromosomal copy number anomalies (duplications and deletions), (3) to display uniparental isodisomy based on loss of heterozygosity (LOH) across genomic regions, (4) to compare paired samples (e.g. tumor and normal), and (5) to generate a file type for viewing SNP data in the University of California, Santa Cruz (UCSC) Human Genome Browser. SNPscan accepts data exported from Affymetrix Copy Number Analysis Tool as its input. We validated SNPscan using data generated from patients with known deletions, duplications, and uniparental disomy. We also inspected previously generated SNP data from 90 apparently normal individuals from the Centre d'Etude du Polymorphisme Humain (CEPH) collection, and identified three cases of uniparental isodisomy, four females having an apparently mosaic X chromosome, two mislabelled SNP data sets, and one microdeletion on chromosome 2 with mosaicism from an apparently normal female. These previously unrecognized abnormalities were all detected using SNPscan. The microdeletion was independently confirmed by fluorescence in situ hybridization, and a region of homozygosity in a UPD case was confirmed by sequencing of genomic DNA. CONCLUSION: SNPscan is useful to identify chromosomal abnormalities based on SNP intensity (such as chromosomal copy number changes) and heterozygosity data (including regions of LOH and some cases of UPD). The program and source code are available at the SNPscan website http://pevsnerlab.kennedykrieger.org/snpscan.htm.

Base Sequence↗
PubMed2004

Genetic abnormalities among severely oligospermic men who are candidates for intracytoplasmic sperm injection.

Recent reports suggest that children born after intracytoplasmic sperm injection performed for male factor infertility are at increased risk of congenital malformations and chromosome aberrations. To explain these observations, we hypothesized that infertile men may be more likely than fertile men to have genetic abnormalities. We studied 750 severely oligozoospermic men (sperm count <5 million/ml) who were candidates for intracytoplasmic sperm injection, and 303 fertile men. We analyzed the peripheral blood karyotype, the Y chromosome long arm for detection of microdeletions in the azoospermia factors, and mutations in the cystic fibrosis gene and the androgen receptor gene. We also analyzed sperm for chromosome aneuploidies among the 421 men who subsequently entered the in vitro fertilization program. A total of 104 genetic abnormalities were diagnosed, corresponding to a frequency of 13.9% (104 of 750). Chromosomal aberrations were present in 5.6% (42 of 750) of infertile men and 0.3% of controls (one of 295), and they were in most cases alterations of the sex chromosomes. Y chromosome long-arm microdeletions were detected in 6.0% (45 of 750) of infertile men and most frequently included the azoospermia factor c, whereas no cases were found in controls (zero of 210). Mutations in the cystic fibrosis gene were diagnosed in 1.2% (nine of 750) of infertile men and 1.0% of controls (three of 303), and mutations in the androgen receptor gene were found in 1.1% (eight of 750) of infertile men and none of the 188 controls. Sperm sex chromosome aneuploidies were increased in men with karyotype anomalies and Y chromosome microdeletions as well as in subjects without constitutional genetic abnormalities. This study shows that the frequency of genetic alterations is increased among men with severe spermatogenic impairment. Genetic tests and genetic counseling should therefore be considered in oligozoospermic men who are candidates for intracytoplasmic sperm injection.

Chromosome Aberrations↗
PubMed2006

Cryptorchidism and semen quality: a TEM and molecular study.

Cryptorchidism is a pathological condition defined as the failure of the testis to descend into the scrotum, the location of the cryptorchid testis can be in the inguinal canal or in the prescrotal and abdominal area, sometimes resulting in atrophic seminiferous tubules. The aim of this study was to analyze semen quality of men who underwent orchidopexy for unilateral or bilateral cryptorchidism during childhood. Semen quality was investigated by light microscopy to evaluate sperm concentration and motility. Sperm morphology was performed by transmission electron microscope (TEM), and the data were mathematically elaborated. The presence of Y microdeletions was investigated by polymerase chain reaction. The effect of cryptorchidism on meiosis was explored by fluorescence in situ hybridization (FISH). The incidence of azoospermia was higher in the group with bilateral compared with unilateral cryptorchidism, and semen parameters were better in the unilateral group. Sperm pathologies detected by TEM indicated a severe deterioration of sperm quality in both groups. Necrosis and apoptosis appeared to be the most frequent pathologies, and their values reached statistical significance compared with those from fertile controls. The presence of chromosome Y microdeletions in patients with cryptorchidism and severe spermatogenetic defects is controversial. No microdeletions were found in this study. FISH values indicated that the mean percentage of gonosome disomies and diploidies were generally out of normal range, indicating a severe disturbance of meiotic segregation. The effects induced by cryptorchidism resolved in childhood seem to include a spermatogenetic impairment, leading to recommendation of detailed ultrastructural and chromosomal sperm analyses before undertaking assisted reproductive techniques.

Adult↗
PubMed2006

Y chromosome and male infertility: update, 2006.

Male factor infertility accounts for about half the cases of couple infertility and in around 50% of cases its etiology remains unknown. Molecular genetic techniques have unveiled a number of etiopathogenetic factors, including microdeletions of the Yq. Y chromosome microdeletions removing the AZoospermia Factor (AZF) regions are the most frequent molecular genetic causes of oligo/azoospermia. The intense effort of many laboratories contributed to a better understanding of the clinical significance of this genetic anomaly and to the identification of fertility candidate genes in the AZF regions. Important progress has been made on the structure of the Y chromosome and the mechanism of deletion. Studies aimed to define a predisposing genetic background for Yq deletions were not successful, perhaps due to the low number of patients analyzed so far. The screening for Yq deletions became a routine diagnostic test that provides an etiology for spermatogenic disturbances, and assess in the prognosis for testicular sperm retrieval according to the type of deletion. Assisted reproductive techniques represent an efficient symptomatic therapy for men bearing Y microdeletions, however, this genetic defect is transmitted to the male offsprings, affecting their fertility. Future studies should focus on understanding the biological function of AZF genes which is an essential step for the development of more appropriate and knowledge-based therapies.

Chromosome Deletion↗
PubMed1999

[Gonadotropin response to GnRH and seminal parameters in low grade varicocele].

The pathogenetic role of varicocele in male infertility is still controversial. Although epidemiological data have clearly shown a higher incidence of varicocele in the population of subfertile and infertile patients, the real effectiveness of the surgical repair of varicocele, expressed as increase in the pregnancy rate, is still debated. The presurgical gonadotropin releasing hormone (GnRH) test is the most reliable predictive index of successful surgical outcome in terms of fertility. Only patients with an increased gonadotropin response (in particular FSH) to GnRH will benefit from the surgery. The aim of the present study was to evaluate the gonadotropin response to GnRH 50 micrograms i.v. in a group of patients with low-medium grade varicocele. At the beginning of the test, a fine needle was inserted into the forearm and kept patent by a saline solution. Blood samples were collected at the following experimental times: 0, +15, +30, +60, +90, +120 min. The stimulus was administered i.v. as bolus at time 0. The gonadotropin response to the stimulus and baseline levels of testosterone, PRL, 17 beta oestradiol and SHBG were compared with those of a control group. Moreover, all the patients underwent semen analysis after 3-7 days' abstinence and to ultrasound-doppler of the testis. Finally, we preliminarily looked for the presence of microdeletions on the Yq chromosome by polymerase chain reaction. No difference in baseline hormonal levels was found between the patients with varicocele and the controls; the LH response to GnRH was also similar in the two groups. The patients with varicocele showed a significantly (p = 0.03) higher FSH response (13.6 +/- 5.9 mUI/ml) to GnRH than controls (3.8 +/- 0.5 mUI/ml). A significant positive correlation (r = 0.6, p = 0.05) was found between LH peaks after GnRH testing and varicocele grade. Nine of 11 patients with varicocele showed significant seminal abnormalities (i.e., oligoasthenospermia): all patients showed a normal karyotype and no microdeletions were detected on the Yq chromosome. The authors underline the importance of presurgical GnRH testing in patients with low grade varicocele, given the close correlation between gonadotropin-stimulated peaks and varicocele grade found in the study. The presence of significant seminal abnormalities, even in patients with low grade varicocele, suggests the use of molecular genetic techniques to detect possible microdeletions on the Yq chromosome, which may be responsible for the infertility.

Adolescent↗
PubMed2001

[DNA analysis of chromosome Y in the area of the azoospermia factor (AZF) in infertile men].

OBJECTIVE: Establishment of investigation of sterile male DNA in AZF region--choice of loci and primers for investigation, optimization of PCR conditions (polymerase chain reaction). DESIGN: For practice. SETTING: Department of Medical Genetics and Foetal Medicine, Faculty of Medicine, Palacky University and Faculty Hospital Olomouc. METHODS: PCR amplification of DNA isolated from blood of sterile men and consequential electrophoresis of synthesized DNA fragments to appoint microdeletions in AZF. RESULTS: From January to June 2000 were detected the microdeletions in AZF of 3 out of 79 sterile men (3.80%) by means of the Experteam firm kit. From July to December 2000 were tested and optimized conditions of amplification of 10 AZF loci to substitute the kit and they were used for examination of the first 20 sterile men of our collection. CONCLUSION: In our laboratory was established routine examination male sterility related to microdeletions in AZF. With our collection of loci was substituted the original Experteam firm kit and was widened spectrum of observed loci.

Base Sequence↗
PubMed2005

Spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome.

BACKGROUND: Sotos syndrome is an overgrowth syndrome with characteristic facial gestalt and mental retardation of variable severity. Haploinsufficiency of the NSD1 gene has been implicated as the major cause of Sotos syndrome, with a predominance of microdeletions reported in Japanese patients. This study was conducted to investigate into the spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome. METHODS: Thirty-six Chinese patients with Sotos syndrome and two patients with Weaver syndrome were subject to molecular testing. RESULTS: NSD1 gene mutations were detected in 26 (72%) Sotos patients. Microdeletion was found in only 3 patients, while the other 23 had point mutations (6 frameshift, 8 nonsense, 2 spice site, and 7 missense). Of these, 19 mutations were never reported. NSD1 gene mutations were not found in the two patients with Weaver syndrome. CONCLUSIONS: Most cases of Sotos syndrome are caused by NSD1 gene defects, but the spectrum of mutations is different from that of Japanese patients. Genotype-phenotype correlation showed that patients with microdeletions might be more prone to congenital heart disease but less likely to have somatic overgrowth. The two patients with Weaver syndrome were not found to have NSD1 gene mutations, but the number was too small for any conclusion to be drawn.

Abnormalities, Multiple↗
PubMed1998

Increased nuchal translucency and CATCH 22.

Recent developments in cytogenetics has shown that 22q11 microdeletion is related to a broad spectrum of malformations which are described under the acronym CATCH 22 (Cardiac, Abnormal faces, Thymic hypoplasia, Cleft palate, Hypocalcaemia and 22 chromosome deletion). We describe a case of a fetus with increased nuchal translucency at 12 weeks' gestation presenting with congenital cardiac defects of DiGeorge syndrome type and hypocalcaemia at birth. The neonate was also diagnosed as carrying the 22q11 microdeletion. When nuchal translucency measurement is increased, CATCH 22 spectrum of malformations should be considered and therefore a thorough karyotype analysis should be performed to exclude microdeletion of chromosome 22.

Adult↗
PubMed2000

Sensorineural hearing loss and Mondini dysplasia caused by a deletion at locus DFN3.

OBJECTIVE: To study a family with inner ear malformations and sensorineural hearing loss. DESIGN: Clinical, radiological, and genetic study of the members of a family with different degrees of sensorineural hearing loss. RESULTS: The males in the family manifested profound congenital hearing loss with severe inner ear malformations, while the only affected female had progressive hearing loss that had begun during puberty. Computed tomography showed inner ear malformations in both males, with enlarged internal auditory meatus and Mondini dysplasia. Genetic analysis disclosed a microdeletion at the locus DFN3 on chromosome X. CONCLUSION: A familial Mondini dysplasia is associated to a microdeletion at the deafness locus DFN3.

Adolescent↗
PubMed1997

Idiopathic thrombocytopenic purpura in two mothers of children with DiGeorge sequence: a new component manifestation of deletion 22q11?

The phenotypic spectrum caused by the microdeletion of chromosome 22q11 region is known to be variable. Nearly all patients with DiGeorge sequence (DGS) and approximately 60% of patients with velocardiofacial syndrome exhibit the deletion. Recent papers have reported various congenital defects in patients with 22q11 deletions. Conversely, some patients have minimal clinical expression. Ten to 25% of parents of patients with DGS exhibit the deletion and are nearly asymptomatic. Two female patients carrying a 22q11 microdeletion and presenting with idiopathic thrombocytopenic purpura are reported. Both had children with typical manifestations of DGS.

Adult↗
PubMed1997

Tricuspid atresia and 22q11 deletion.

Tricuspid atresia has not been reported in 22q11 microdeletions causing DiGeorge and velo-cardio-facial syndromes. We investigated the prevalence of 22q11 hemizygosity in 26 children with tricuspid atresia. Fluorescent hybridization with the Sc11.1 probe demonstrated a 22q11 microdeletion in 2 patients, one with and another without transposition of the great arteries. Both deletion patients had minor facial anomalies characteristic of DiGeorge syndrome. The present observations suggest that tricuspid atresia should be included in the list of cardiac malformations seen in del22q11 syndromes.

Adult↗
PubMed1998

Molecular confirmation of germ line mosaicism for a submicroscopic deletion of chromosome 22q11.

Submicroscopic deletions of chromosome 22q11 have been reported in a multiple anomaly syndrome variously labelled as velocardiofacial syndrome, conotruncal anomaly face syndrome, and Di George syndrome. Most 22q11 microdeletions occur sporadically, although in some cases the deletion may be transmitted. We describe two affected sibs with confirmed 22q11 deletions from unaffected parents who are not deleted. Haplotype analysis demonstrates that the deletion in the affected sibs has occurred on the same maternal chromosome 22. Furthermore, an unaffected sib was found to have inherited the same maternal haplotype at 22q11 in an undeleted form. This is the first molecular demonstration of germ line mosaicism for a microdeletion at chromosome 22q11 and highlights the need for caution in estimation of recurrence risks, even when constitutional deletions have been excluded on parental analysis.

Chromosome Deletion↗