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At least 289 records · Page 16Linked to original sources
PubMed1991

Isolated lissencephaly sequence associated with a microdeletion at chromosome 17p13.

DNA markers YNZ22.1, YNH37.3, 144D6 and VAW508 were studied in a patient with the isolated lissencephaly sequence (ILS). A normal karyotype was found in the patient. The DNA of the patient showed deletions of markers YNZ22.1 and YNH37.3. This is the first report of a case of ILS (with grade 3 lissencephaly) with a submicroscopic deletion. The presence of a microdeletion in 17p13 in an ILS patient indicates that Miller-Dieker syndrome and ILS have a common etiology.

Blotting, Southern↗
PubMed1991

A case of Hirschsprung disease with a chromosome 13 microdeletion, del(13)(q32.3q33.2): potential mapping of one disease locus.

A mentally retarded boy with discrete physical findings, Hirschsprung disease (HD) and a microdeletion of 13q,del(13)(q32.3q33.2) is described. Band 13q33.1 was consistently missing in all cells. There have been, to date, 4 published cases of deletions involving the long arm of chromosome 13 associated with HD: the interstitial deletion reported here is much smaller than, and it partially overlaps with, the previously reported deletions; it could be helpful for mapping one of the genes involved in this disease.

Adolescent↗
PubMed1991

Characterisation of a Xp21 microdeletion syndrome in a 2-year-old boy with muscular dystrophy, glycerol kinase deficiency and adrenal hypoplasia congenita.

We report a 2-year-old boy with Duchenne muscular dystrophy (DMD), glycerol kinase deficiency (GK) and adrenal hypoplasia congenita (AHC). At three weeks of age, the patient was hospitalized for the first time with symptoms of hypotone dehydration because of AHC. At present, he shows severe muscular hypotonia and developmental delay. The patient and his family were referred to us for prenatal diagnosis and carrier testing in the mother of the patient and the mother's sister, respectively. The patient's DNA was examined by Southern blot and polymerase chain reaction analyses, using cDNA and genomic probes within and around the dystrophin (DYS) locus. A deletion was revealed, spanning DXS28, the whole dystrophin locus, DXS84 and DXS148, whereas DXS67, DXS68 (pter) and OTC (cen) were found to be retained. The cytogenetically visible microdeletion was also seen in the patient's mother, but not in the mother's sister or the patient's maternal grandmother. Our findings support the locus order pter-DXS67-DXS68-DXS28-AHC-GK-DMD-cen.

Adrenal Insufficiency↗
PubMed1993

Physical mapping of microdeletions of the chromosome 17 short arm associated with Smith-Magenis syndrome.

We used probes from the juxta-centromeric region of the chromosome 17 short arm to map three microdeletions in patients with Smith-Magenis syndrome. The common clinical findings were: speech delay with behavioural problems associated with broad flat midface, brachycephaly, broad nasal bridge and brachydactyly. We demonstrated, using Southern blot analysis (loss of heterozygosity and gene dosage), that all patients were deleted for two p11.2 markers: pYNM 67-R5 (D17S29) and pA10-41 (D17S71). We determined that one breakpoint was located between D17S58 and D17S29 and the other breakpoint distal to D17S71. The possibility that an unstable region, located between the Smith-Magenis syndrome locus and CMT1A a closely located locus, could be involved in the rearrangements associated with these two inherited diseases is discussed.

Abnormalities, Multiple↗
PubMed1986

Hypomelanosis of Ito (incontinentia pigmenti achromians) and mosaicism for a microdeletion of 15q1.

Hypomelanosis of Ito (incontinentia pigmenti achromians), a sacrococcygeal complex dysembryoma, seizures, severe cerebral lesions, mental retardation, chorioretinal atrophy, hemihypotrophy of the body, and skeletal anomalies are reported in a female infant of North African origin. Karyotype analysis revealed mosaicism for a microdeletion of the proximal region of 15q similar to that observed in Willi-Prader syndrome. The possibility of gene assignment of Ito's disease or that it may represent a nonspecific marker for mosaicism are discussed.

Chromosome Banding↗
PubMed1988

Zellweger syndrome and a microdeletion of the proximal long arm of chromosome 7.

A 16-day-old girl with Zellweger syndrome and a chromosomal rearrangement, 46,XX,del(7)(q11.22q11.23), is reported. The diagnosis was confirmed by marked deficiencies of peroxisomal beta-oxidation enzymes and dihydroxyacetone phosphate acyltransferase activities in rectal cells and fibroblasts obtained by biopsy and in hepatic cells obtained at autopsy. This is the first report of Zellweger syndrome associated with a chromosomal arrangement, a microdeletion of chromosome 7. A tentative gene assignment to 7q11 is suggested.

Chromosome Banding↗
PubMed1996

Routine screening for microdeletions by FISH in 77 patients suspected of having Prader-Willi or Angelman syndromes using YAC clone 273A2 (D15S10).

About 70% of patients with Prader-Willi syndrome (PWS) and Angelman syndrome (AS) have a common interstitial de novo microdeletion encompassing paternal (PWS) or maternal (AS) loci D15S9 to D15S12. Most of the non-deletion PWS patients and a small number of non-deletion AS patients have a maternal or paternal uniparental disomy (UPD) 15, respectively. Other chromosome 15 rearrangements and a few smaller atypical deletions, some of the latter being associated with an abnormal methylation pattern, are rarely found. Molecular and fluorescence in situ hybridization (FISH) analysis have both been used to diagnose PWS and AS. Here, we have evaluated, in a typical routine cytogenetic laboratory setting, the efficiency of a diagnostic strategy that starts with a FISH deletion assay using Alu-PCR (polymerase chain reaction)-amplified D15S10-positive yeast artificial chromosome (YAC) 273A2. We performed FISH in 77 patients suspected of having PWS (n = 66) or AS (n = 11) and compared the results with those from classical cytogenetics and wherever possible with those from DNA analysis. A FISH deletion was found in 16/66 patients from the PWS group and in 3/11 patients from the AS group. One example of a centromere 15 co-hybridization performed in order to exclude cryptic translocations or inversions is given. Of the PWS patients, 14 fulfilled Holm's criteria, but two did not. DNA analysis confirmed the common deletion in all patients screened by the D15S63 methylation test and in restriction fragment length polymorphism dosage blots. In 3/58 non-deletion patients, other chromosomal aberrations were found. Of the non-deleted group, 27 subjects (24 PWS, 3 AS) were tested molecularly, and three patients with an uniparental methylation pattern were found in the PWS group. The other 24/27 subjects had neither a FISH deletion nor uniparental methylation, but two had other cytogenetic aberrations. Given that cytogenetic analysis is indispensable in most patients, we find that the FISH deletion assay with YAC 273A2 is an efficient first step for stepwise diagnostic testing and mutation-type analysis of patients suspected of having PWS or AS.

Adolescent↗
PubMedDate not supplied

Isolated innominate artery in 22q11 microdeletion.

A patient with an isolated left innominate artery (with a right-sided cervical aortic arch) is described. This is the first report of such an anomaly associated with chromosome 22q11 microdeletion. The abnormality represents an interruption in the primitive aortic arch that is atypical for this chromosome deletion.

Brachiocephalic Trunk↗
PubMed1990

Molecular and cytogenetic analysis in two patients with microdeletions of 7p and Greig syndrome: hemizygosity for PGAM2 and TCRG genes.

Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder that has been mapped to 7p13. We have investigated two patients with GCPS and a cytogenetically visible microdeletion of the short arm of chromosome 7 with gene probes that have been assigned close to the proposed Greig locus. Deletion breakpoints were determined from high-resolution G- and R-banded chromosomes. In patient BC with a de novo deletion (7p12.3-7p14.2) we have found a loss of the genomic region containing the T-cell receptor gamma (TCRG) gene cluster, whereas the other patient IR with a deletion (7p11.2-7p13) due to a de novo translocation was apparently normal for this region. Gene dosage analysis revealed a loss of the phosphoglycerate mutase muscular form (PGAM2) gene locus in both patients. Hox 1.4 and interferon-beta 2 (IFNB2) showed a normal gene dosage. Our investigations revealed the following ordering and assignments of the studied genes: PGAM2 and GCPS in 7p12.3-13; TCRG in the distal part of 7p13-7p14.2; Hox 1.4 and IFNB2 distal to 7p14.2. Our results suggest a location of the TCRG gene more proximal than that reported previously. Furthermore, we were able to exclude the Hox 1.4 gene from involvement in the pathogenesis of GCPS.

Bisphosphoglycerate Mutase↗
PubMed1991

Microdeletions within 22q11 associated with sporadic and familial DiGeorge syndrome.

DiGeorge syndrome (DGS) is a developmental field defect of the third and fourth pharyngeal pouches. It is associated with deletion of 22q11 in 11% of cases. Molecular genetic analysis with probes from 22q11-pter reveals that a subset of markers is hemizygous in DGS patients with normal karyotypes. There is no apparent difference in the phenotype or the severity of the disorder between patients with the smallest detectable submicroscopic deletion and those with the largest cytogenetically visible abnormality. A microdeletion was found in a mildly affected child and in the severely affected child of a mildly affected father. Dysmorphology, especially cardiac outflow tract anomalies, resulting from 22q11 deletion may be more common than currently realized since chromosomes are unlikely to be checked if the complete spectrum of DGS is not present. Antenatal diagnosis, through detection of hemizygosity at 22q11, will be a possibility for mildly affected parents unwilling to risk the birth of a severely affected child.

Cell Line↗
PubMedDate not supplied

Meiotic studies of infertile men in case of non-obstructive azoospermia with normal karyotype and no microdeleted Y-chromosome precise the clinical couple management.

To identify meiotic criteria for infertility management in non-obstructive azoospermic men, a prospective and multicentric study was organized in Andrological Departments of Paris (France), Roma (Italy) and Budapest (Hungary). In 117 non-obstructive azoospermic men with normal karyotype and no Y-chromosome microdeletion, histology and meiotic studies on bilateral bipolar testicular biopsies were done. Histologically, 40 patients (34%) presented spermatocyte or spermatid arrest, 39 (33%) hypospermatogenesis whereas no meiotic cell could be observed in the remaining patients (33%). Cytogenetically, meiotic figures could only be obtained from the two first histological groups. Meiotic abnormalities were observed in a total of 44 patients (37.6%) including nine patients (7.7%) with severe class I and class IIB anomalies and 19 patients (16.2%) with class IIC environmentally linked meiotic abnormalities. These results provided essential clues for an accurate clinical management. For patients with no meiotic figures and patients with class I and class IIB anomalies, an hormonal stimulation is illusory and a sperm gift should be directly proposed. An hormonal stimulation should be proposed to all the other patients, either directly or following the treatment of the testicular microenvironment for the patients presenting class IIC anomalies. The genetic risk and possibility of prenatal chromosomal analysis in case of pregnancy should be clearly exposed to all the couples in all the cases where type IIA, III or IV anomalies are present. This therapeutical strategy has been applied to all the patients in our series.

Chromosomes, Human, Y↗
PubMedDate not supplied

Chromosome 22q11.2 microdeletion in a patient with hemophilia A.

We report a 6-year-old patient with hemophilia A, who also exhibited clinical features typical of 22q11.2 deletion syndrome (22qDS). The specific traits were mild mental retardation, speech delay, hypernasal speech, deficits in voice quality and articulation, narrow palpebral fissures, broad and depressed nasal root, high-arched palate, microstomia, and overfolded ears. The patient had no associated congenital cardiac or palatal malformations. It can be particularly difficult to identify this syndrome in newborns and infants without congenital heart defects. This case underlines that microdeletion of chromosome 22q11.2 should be considered in any patient who exhibits typical clinical features of 22qDS, regardless of whether they have another single-gene disorder.

Bone Diseases↗
PubMed2004

Gonadotropin treatment of an azoospermic patient with a Y-chromosome microdeletion.

OBJECTIVE: To report on the treatment with recombinant FSH of an azoospermic normogonadotropic patient with a Y-chromosome microdeletion. DESIGN: Case report. SETTING: An assisted reproduction center. PATIENT(S): A 32-year-old patient with azoospermia. INTERVENTION(S): Histological testicular biopsy, Y-chromosome screening, FSH treatment, and intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S): Fertilization, embryo development, pregnancy, and delivery. RESULT(S): After 6 months of treatment with gonadotropins, a small number of spermatozoa were found in the patient's ejaculate and used for IVF, resulting in a successful twin pregnancy and the delivery of two healthy girls. CONCLUSION(S): In this study, treatment with gonadotropins promoted the spermatogenesis process and led to the production of spermatozoa in a normogonadotropic azoospermic patient.

Adult↗
PubMed2005

A survey of the 22q11 microdeletion in a large cohort of schizophrenia patients.

The occurrence of a microdeletion at 22q11 has long been considered to constitute a risk factor for schizophrenia. Higher rates of 22q11 deletions have been reported in cohorts of patients with schizophrenia. In order to estimate the prevalence of the 22q11 deletion in schizophrenia patients more accurately, a screening for 22q11 deletions was conducted on a cohort of 634 schizophrenia patients, the largest sample size screened to date. Seven microsatellites and three SNPs were used to assess the deletion genotype. In cases where all markers were found to be homozygous (hemizygous), the individual was assumed to carry the deletion. The method used here is simple and efficient in comparison with hybridization technologies. Moreover, the rate of false positives is very low (P-value in the range of 10(-4) to 10(-3)). Approximately 1% of the patient cohort was found to carry 22q11 deletions.

Adolescent↗
PubMed2005

Uncommon Alu-mediated NF1 microdeletion with a breakpoint inside the NF1 gene.

Neurofibromatosis type 1 (NF1) microdeletion syndrome is caused by haploinsufficiency of the NF1 gene and of gene(s) located in adjacent flanking regions. Most of the NF1 deletions originate by nonallelic homologous recombination between repeated sequences (REP-P and -M) mapped to 17q11.2, while a few uncommon deletions show unusual breakpoints. We characterized an uncommon 1.5-Mb deletion of an NF1 patient displaying a mild phenotype. We applied high-resolution FISH analysis allowing us to obtain the sequence of the first junction fragment of an uncommon deletion showing the telomeric breakpoint inside the IVS23a of the NF1 gene. Sequence analysis of the centromeric and telomeric boundaries revealed that the breakpoints were present in the AluJb and AluSx regions, respectively, showing 85% homology. The centromeric breakpoint is localized inside a chi-like element; a few copies of this sequence are also located very close to both breakpoints. The in silico analysis of the breakpoint intervals, aimed at identifying consensus sequences of several motifs usually involved in deletions and translocations, suggests that Alu sequences, probably associated with the chi-like element, might be the only recombinogenic motif directly mediating this large deletion.

Alu Elements↗
PubMedDate not supplied

Patent ductus arteriosus and microdeletion 22q11 in a patient with Klinefelter syndrome.

We describe an uncommon association of deletion 22q11 in a patient with Klinefelter syndrome. Even though congenital heart defects (CHD) are not associated with Klinefelter syndrome, further investigation of this patient with patent ductus arteriosus showed a microdeletion of chromosome 22q11.2. While this finding may be coincidental, it is important to further evaluate patients when the clinical features are suggestive of a secondary abnormality.

Adult↗
PubMedDate not supplied

Microdissection and reverse painting reveals a microdeletion 6(q26qter) in a de novo r(6) chromosome.

Ring chromosomes 6 are rare constitutional abnormalities with inconsistent phenotypic and clinical features. One of the reasons for this variability is the cytogenetically undetectable loss of chromosomal material from the telomeric segments at 6p or 6q. We have therefore used fluorescence in situ hybridization (FISH) to analyse a ring chromosome 6 that was detected in a newborn boy with dysmorphic features. Reverse painting of the microdissected ring chromosome onto normal metaphase spreads revealed a small deletion of the terminal region of the long arm, 6(q26qter). Moreover, the simple all-telomeric sequence (TTAGG)n was lost, whereas the p-specific subtelomeric sequence was still present. Our findings confirm that microdeletions occur during the formation of r(6) chromosomes and, therefore, are an important determinator of the associated phenotype.

Adult↗
PubMed2001

A dysfunctional factor X (factor X San Giovanni Rotondo) present at homozygous and double heterozygous level: identification of a novel microdeletion (delC556) and missense mutation (Lys(408)-->Asn) in the factor X gene. A study of an Italian family.

Low levels of factor X (F.X) were detected in a 4-year-old boy who experienced acute lymphoblastic leukemia and bleeding manifestations. Laboratory data suggested the presence of a dysfunctional F.X molecule. Two novel F.X gene mutations were identified in the proband that was double heterozygous for both: a microdeletion (delC556) in exon VI resulting in a frameshift leading to a termination codon at position 226. This deletion was found in six family members with reduced F.X antigen and activity levels. A second mutation characterised by a G(1344)-->C transversion in exon VIII was detected in the proband resulting in a Lys(408)-->Asn substitution. This latter mutation was present in several asymptomatic family members from the paternal and the maternal side. The proband's sister was homozygous for the Lys(408)-->Asn substitution and exhibited low F.X activity with a normal antigen level. The naturally occurring F.X Lys(408)-->Asn (F.X(K408N)) variant was isolated from plasma of either homozygous or double heterozygous individuals. NH(2)-terminal sequencing of the heavy chain of F.X(K408N) failed to show any sequence abnormality in patients who were also carriers of the delC556, suggesting that this latter lesion accounted for the lack of F.X synthesis. Purified F.X Lys(408)-->Asn had an identical behaviour to normal F.X as judged by SDS-PAGE and immunoblotting. Clotting assay using purified F.X(K408N) and F.X-deficient plasma resulted in a laboratory phenotype similar to that observed in a homozygous subject for F.X Lys(408)-->Asn substitution. This is the first characterisation of a naturally occurring F.X variant with a mutation at the COOH-terminal end of the molecule.

Amino Acid Sequence↗