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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genosensor Array 300 (Abbott) is a multiplex platform for array-based comparative genomic hybridization that detects unbalanced genomic aberrations including whole chromosome gains/losses, microdeletions, duplications and unbalanced subtelomeric rearrangements. A series of 30 patients with unexplained mental retardation, dysmorphic features, congenital abnormalities and normal high resolution karyotype and FISH subtelomeric studies were analyzed using Genosensor Array 300 array-CGH. We identified a chromosomal aberration in one patient with an interstitial 1p31.1 deletion. FISH analysis with BACs specific probes of the 1p region confirmed the interstitial 1p22.2-p31.1 deletion. The patient was a 20-year-old man with short stature, facial dysmorphism including asymmetry, scoliosis, severe psychomotor delay and an epibulbar dermoid cyst. The phenotype was compatible with Goldenhar syndrome despite the absence of asymmetric ears. This observation is of interest since it could be a clue in the search for the genes responsible for Goldenhar syndrome. This study demonstrates the utility of the array-CGH technology in detecting interstitial deletions.
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PMID:Array-CGH in a series of 30 patients with mental retardation, dysmorphic features, and congenital malformations detected an interstitial 1p22.2-p31.1 deletion in a patient with features overlapping the Goldenhar syndrome. 1862 84

Subtelomeric imbalances are a significant cause of congenital disorders. Screening for these abnormalities has traditionally utilized GTG-banding analysis, fluorescence in situ hybridization (FISH) assays, and multiplex ligation-dependent probe amplification. Microarray-based comparative genomic hybridization (array-CGH) is a relatively new technology that can identify microscopic and submicroscopic chromosomal imbalances. It has been proposed that an array with extended coverage at subtelomeric regions could characterize subtelomeric aberrations more efficiently in a single experiment. The targeted arrays for chromosome microarray analysis (CMA), developed by Baylor College of Medicine, have on average 12 BAC/PAC clones covering 10 Mb of each of the 41 subtelomeric regions. We screened 5,380 consecutive clinical patients using CMA. The most common reasons for referral included developmental delay (DD), and/or mental retardation (MR), dysmorphic features (DF), multiple congenital anomalies (MCA), seizure disorders (SD), and autistic, or other behavioral abnormalities. We found pathogenic rearrangements at subtelomeric regions in 236 patients (4.4%). Among these patients, 103 had a deletion, 58 had a duplication, 44 had an unbalanced translocation, and 31 had a complex rearrangement. The detection rates varied among patients with a normal karyotype analysis (2.98%), with an abnormal karyotype analysis (43.4%), and with an unavailable or no karyotype analysis (3.16%). Six patients out of 278 with a prior normal subtelomere-FISH analysis showed an abnormality including an interstitial deletion, two terminal deletions, two interstitial duplications, and a terminal duplication. In conclusion, genomic imbalances at subtelomeric regions contribute significantly to congenital disorders. Targeted array-CGH with extended coverage (up to 10 Mb) of subtelomeric regions will enhance the detection of subtelomeric imbalances, especially for submicroscopic imbalances.
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PMID:Identification of chromosome abnormalities in subtelomeric regions by microarray analysis: a study of 5,380 cases. 1866 43

Pericentric inversions of chromosome 19 are very rare rearrangements. Only one case was shown to have resulted in duplication deficiency in the offspring. We report a familial case of pericentric inversion of chromosome 19 not detectable by standard karyotype and usual subtelomeric FISH probes. This inversion was transmitted in its balanced and in its recombinant form to the offspring. The two children carrying the recombinant chromosome 19 presented with growth and mental retardation, microcephaly, mild facial dysmorphism and clinodactyly. The recombinant chromosome 19 was characterized by FISH and array CGH. It consisted of a 400kb 19pter deletion and a 6.9Mb (19q13.33-qter) duplication. This observation supports the recombination risk of pericentric inversion of chromosome 19 and emphasizes the role of molecular cytogenetics techniques in the characterization of chromosome 19 rearrangements.
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PMID:Monosomy 19pter and trisomy 19q13-qter in two siblings arising from a maternal pericentric inversion: clinical data and molecular characterization. 1867 48

We report on a 25-year-old male with mental retardation and global developmental delay, low levels of total and LDL cholesterol and dysmorphism, which includes macrocephaly, hypertelorism, synophrys, telecanthus, prominent philtrum, low set ears, bilateral cataracts, bilateral cleft lip with cleft palate and widely spaced nipples. While his karyotype and subtelomeric FISH studies were normal, a de novo, 5.4 Mb interstitial deletion at 1p32 [del(1)(p32.2-p32.3)] was identified by oligonucleotide aCGH. The deleted region encompasses a cluster of genes involved in fatty acid oxidation and cholesterol metabolism. One of these genes is PCSK9, a key regulator for a number of cell-surface LDL receptors. In addition to the loss of the paternal allele, our patient is hemizygous for the A443T weak loss-of-function mutation in exon 8 of PCSK9. Loss-of-function mutations within PCSK9 have been shown to cause hypocholesterolemia. Another gene also mapped to this region and deleted in this patient is DAB1, reported to be involved in brain development. Based on the findings in the current patient and in the four previously reported individuals with del(1)(p32.2-p32.3), we suggest that these patients may have a new microdeletion syndrome that may have gone undetected because of its location in a G-negative band. However, the condition can easily be identified by array-CGH.
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PMID:Deletion (1)(p32.2-p32.3) detected by array-CGH in a patient with developmental delay/mental retardation, dysmorphic features and low cholesterol: A new microdeletion syndrome? 1868 Jan 92

We report on a 16-year-old girl with a multiple congenital anomalies/mental retardation condition, in which a 1.7 Mb tandem duplication of chromosome region 16p13.3 was detected by array-CGH. Mental retardation was moderate (IQ 45), with very limited speech. She had tall stature with relative microcephaly. Clinical manifestations included distinctive facial appearance with deep set eyes, narrow palpebral fissures, wide nasal bridge, long philtrum, rounded nasal tip, thin upper lip, protruding mandible and abnormal auricles, hand and foot anomalies. The causal 16p13.3 duplication is one of the smallest reported so far, and includes the CBP gene, whose haploinsufficiency is responsible for the Rubinstein-Taybi syndrome. By comparing clinical manifestations of our patient with those of patients carrying similar rearrangements, we could infer that 16p13.3 microduplications encompassing the Rubinstein-Taybi region result in a recognizable clinical condition, most likely representing a single gene disorder.
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PMID:Duplication of the Rubinstein-Taybi region on 16p13.3 is associated with a distinctive phenotype. 1868 73

Recent advances in molecular cytogenetics enable identification of small chromosomal aberrations that are undetectable by routine chromosome banding in 5-20% of patients with mental retardation/developmental delay (MR/DD) and dysmorphism. The aim of this study was to compare the clinical usefulness of two molecular cytogenetic techniques, metaphase high-resolution comparative genomic hybridization (HR-CGH) and targeted array CGH, also known as Chromosomal Microarray Analysis (CMA). A total of 116 patients with unexplained mild to severe MR and other features suggestive of a chromosomal abnormality with apparently normal or balanced karyotypes were analyzed using HR-CGH (43 patients) and/or CMA (91 patients). Metaphase HR-CGH detected seven interstitial deletions (16.3%). Rare deletions of chromosomes 16 (16p11.2p12.1) and 8 (8q21.11q21.2) were identified. Targeted CMA revealed copy-number changes in 19 of 91 patients (20.8%), among which 11 (11.8%) were clinically relevant, 6 (6.5%) were interpreted as polymorphic variants and 2 (2.1%) were of uncertain significance. The changes varied in size from 0.5 to 12.9 Mb. In summary, our results show that metaphase HR-CGH and array CGH techniques have become important components in cytogenetic diagnostics, particularly for detecting cryptic constitutional chromosome imbalances in patients with MR, in whom the underlying genetic defect is unknown. Additionally, application of both methods together increased the detection rates of genomic imbalances in the tested groups.
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PMID:Application of metaphase HR-CGH and targeted Chromosomal Microarray Analyses to genomic characterization of 116 patients with mental retardation and dysmorphic features. 1869 22

Clinical manifestations of Jacobsen syndrome (JBS) depend on the size of the 11qter deletion, which usually varies between approximately 7 and 20 Mb. Typical JBS features include developmental delay/mental retardation, short stature, congenital heart defects, thrombocytopenia, and characteristic dysmorphic facial features. We report on a family in which a 4-year-old girl as well as her mother and maternal uncle present with subtle features of JBS. Notably, neither thrombocytopenia nor congenital anomalies were detected in this family. Cytogenetic analyses revealed normal karyotypes. Using fluorescence in situ hybridization (FISH) and whole-genome oligonucleotide array CGH analyses, we identified an approximately 5 Mb deletion of the terminal part of chromosome 11q in all the three affected family members. The deletion breakpoint was mapped between 129,511,419 and 129,519,794 bp. This is the smallest deletion reported in a JBS patient. Interestingly, the FLI1 (friend leukemia virus integration 1) hematopoiesis factor gene located approximately 6.5 Mb from 11qter and usually deleted in patients with JBS, is intact. Our data support previous hypotheses that FLI1 haploinsufficiency is responsible for thrombocytopenia in patients with JBS.
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PMID:Clinical and molecular-cytogenetic evaluation of a family with partial Jacobsen syndrome without thrombocytopenia caused by an approximately 5 Mb deletion del(11)(q24.3). 1879 74

Cornelia de Lange syndrome (CdLS) is a rare, multiple congenital anomaly/mental retardation syndrome characterized by varied clinical signs including facial dysmorphism, pre- and post-natal growth defects, small hands and malformations of the upper limbs. Established genetic causes include mutations in the NIPBL (50-60%), SMC1L1 and SMC3 (5%) genes. To detect chromosomal rearrangements pointing to novel positional candidate CdLS genes, we used array-CGH to analyze a subgroup of 24 CdLS patients negative for mutations in the NIPBL and SMC1L1 genes. We identified three carriers of DNA copy number alterations, including a de novo 15q26.2-qter 8-Mb deletion, and two inherited 13q14.2-q14.3 1-Mb deletion and 13q21.32-q21.33 1.5-Mb duplication, not reported among copy number variants. The clinical presentation of all three patients matched the diagnostic criteria for CdLS, and the phenotype of the patient with the 15qter deletion is compared to that of both CdLS and 15qter microdeletion patients.
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PMID:Search for genomic imbalances in a cohort of 24 Cornelia de Lange patients negative for mutations in the NIPBL and SMC1L1 genes. 1879 46

We describe a 14-year-old boy with congenital bilateral cataracts, blepharophimosis, ptosis, choanal atresia, sensorineural hearing loss, short, webbed neck, poor esophageal motility, severe growth and mental retardation, skeletal anomalies, seizures, and no speech. As an infant, he had transient hypogammaglobulinemia requiring IVIG therapy. Cytogenetic studies show an apparently de novo visible duplication at 1p36.3. Fluorescence in situ hybridization (FISH) studies confirm that the common region for the 1p36 deletion syndrome (p58) is duplicated. Probes for D1Z2 at 1p36.3 and the subtelomeric region of 1p (TEL1p) are also duplicated. Array comparative genomic hybridization (aCGH) studies were done at three separate laboratories, each with somewhat different results. BAC whole genome array CGH suggests a single clone gain at the 1p terminus and a single clone deletion at 1p36.3. A targeted BAC array panel with higher resolution at the distal 1p36 region detects a telomeric duplication and an interstitial deletion. Oligonucleotide whole genomic aCGH shows the highest resolution and a more complex rearrangement: two duplications, an interstitial deletion, and a normal region. The MMP23A/B "matrix metalloproteinase 23A/B" genes are within the distal duplication region in our patient, and this patient does not have craniosynostosis. This is the first association of congenital cataracts, choanal atresia, and transient immune abnormalities with 1p36 duplication/deletion. This case illustrates the limitations of different cytogenetic technologies, and shows how three separate aCGH platforms allow for refined delineation and interpretation of the complex cytogenetic rearrangement which would not have been discovered by standard high-resolution chromosome analysis.
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PMID:Cytogenetic and array CGH characterization of de novo 1p36 duplications and deletion in a patient with congenital cataracts, hearing loss, choanal atresia, and mental retardation. 1892 66

A ring X chromosome is found in about 6% of patients with Turner syndrome (TS), often with mosaicism for a 45,X cell line. Patients with this karyotype are reported to have a higher incidence of a more severe phenotype including mental retardation. In fact, some studies have shown a correlation between this severity and the presence or absence of an intact and functional X inactivation center (XIST). However, the phenotype of the individuals with r(X) cannot be entirely defined in terms of their X-inactivation patterns. Nevertheless, a small group of these patients have been described to manifest clinical features reminiscent of the Kabuki syndrome. Here we present a female patient with clinical features resembling Kabuki syndrome and a mos 45,X/46,X,r(X) karyotype. Methylation analyses of polymorphic alleles of the androgen receptor gene showed that both alleles were unmethylated suggesting an active ring chromosome. A specific X chromosome array CGH was performed estimating the size of the ring to be 17 Mb, lacking the XIST gene, and including some genes with possible implications in the phenotype of the patient.
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PMID:A small and active ring X chromosome in a female with features of Kabuki syndrome. 1892 62


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