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

Deletions of chromosome bands 13q33-34 are rare. Patients with such deletions have mental retardation, microcephaly, and distinct facial features. Male patients frequently also have genital malformations. We report on four patients with three overlapping deletions of 13q33-34 that have been characterized by tiling-path array-CGH. Patient 1 had mental retardation and microcephaly with an interstitial 4.7 Mb deletion and a translocation t(12;13)(q13.3;q32.3). His mother (Patient 2), who also had mental retardation and microcephaly, carried the identical chromosome aberration. Patient 3 was a girl with a de novo insertion ins(7;13)(p15.1;q22q31) and interstitial 4.5 Mb deletion in 13q33-34. She had mental retardation and microcephaly. Patient 4 was a newborn boy with severe genital malformation (penoscrotal transposition and hypospadias) and microcephaly. He had a de novo ring chromosome 13 lacking the terminal 9.3 Mb of 13q. Karyotype-phenotype comparisons of these and eight previously published del13q33-34 patients suggest EFNB2 as a candidate gene for genital malformations in males. Molecular cytogenetic definition of a common deleted region in all patients suggests ARHGEF7 as a candidate gene for mental retardation and microcephaly.
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PMID:Chromosome deletions in 13q33-34: report of four patients and review of the literature. 1820 71

Alopecia-contractures-dwarfism mental retardation syndrome (ACD syndrome; OMIM 203550) is a very rare genetic disorder with distinct features. To our knowledge, there have been four cases documented to date. In addition, another three patients, previously described as having IFAP syndrome (OMIM %308205), may also have ACD syndrome. We report on one patient with short stature, total alopecia, ichthyosis, photophobia, seizures, ectrodactyly, vertebral anomalies, scoliosis, multiple contractures, mental retardation, and striking facial and other features (e.g. microdolichocephaly, missing eyebrows and eyelashes, long nose, large ears) consistent with ACD syndrome. Results of laboratory testing in the literature case reports were normal, although in none of them, array-CGH (microarray-based comparative genomic hybridization) analysis was performed. In conclusion, the combination of specific features, including total alopecia, ichthyosis, mental retardation, and skeletal anomalies are suggestive of ACD syndrome. We propose that children with this syndrome undergo a certain social pediatric protocol including EEG diagnostics, ophthalmological investigation, psychological testing, management of dermatologic and orthopedic problems, and genetic counseling.
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PMID:Expanding the phenotype of alopecia-contractures-dwarfism mental retardation syndrome (ACD syndrome): description of an additional case and review of the literature. 1820 61

We report on a 4-year-old male with an interstitial tandem duplication of Xq21.1-q21.31 who presented with clinical features of Prader-Willi syndrome (PWS). The duplication was maternally inherited. Abnormalities of the X chromosome have previously been reported in association with a PWS phenotype, but to date, specific duplications of Xq21.1-q21.31 have not. We refined the chromosomal breakpoints seen on initial G-banded karyotyping in our case with comparative genomic hybridization by microarray (array CGH). The duplication was between 11.1 and 14.4 Mb in length and overlaps with three loci to which mental retardation with PWS-like features have been previously mapped, showing the utility of array CGH in helping to identify candidate genes. We conclude that duplication of chromosomal region Xq21.1-q21.31 potentially results in a PWS-like phenotype. Reviewing the literature on similar duplications, we further conclude that distal Xq duplications can result in features typically seen in infants with PWS, while proximal duplications can result in features typically seen in older children and adults with PWS. Duplications of chromosome Xq should be considered in the differential diagnosis of PWS, especially in males.
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PMID:Prader-Willi syndrome phenocopy due to duplication of Xq21.1-q21.31, with array CGH of the critical region. 1827 35

Complex chromosomal rearrangements [CCRs] are considered very rare, but are being detected with an increasing frequency because of the enhanced resolution of novel molecular karyotyping techniques like array-CGH. This report describes a patient carrying a unique CCR involving one duplication and two triplications in a 3.2 Mb region on 19p13.11. The patient presented with microcephaly, velopharyngeal insufficiency, dysmorphism, mental retardation and a muscular ventricular septal defect. We show that CCRs are likely to be more frequent than hitherto appreciated. This has important consequences for genotype-phenotype correlations and warrants caution before labelling imbalances as "simple".
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PMID:A complex submicroscopic chromosomal imbalance in 19p13.11 with one microduplication and two microtriplications. 1828 19

For several decades etiological diagnosis of patients with idiopathic mental retardation (MR) and multiple congenital anomalies (MCA) has relied on chromosome analysis by karyotyping. Conventional karyotyping allows a genome-wide detection of chromosomal abnormalities but has a limited resolution. Recently, array-based comparative genomic hybridization (array CGH) technologies have been developed to evaluate DNA copy-number alterations across the whole-genome at a much higher resolution. It has proven to be an effective tool for detection of submicroscopic chromosome abnormalities causing congenital disorders and has recently been adopted for clinical applications. Here, we investigated four high-density array platforms with a theoretical resolution < or =100 kb: 33K tiling path BAC array, 500K Affymetrix SNP array, 385K NimbleGen oligonucleotide array and 244K Agilent oligonucleotide array for their robustness and implementation in our diagnostic setting. We evaluated the practical performance based on the detection of 10 previously characterized abnormalities whose size ranged from 100 kb to 3 Mb. Furthermore, array data analysis was performed using four computer programs developed for each corresponding platform to test their effective ability of reliable copy-number detection and their user-friendliness. All tested platforms provided sensitive performances, but our experience showed that accurate and user-friendly computer programs are of crucial importance for reliable copy-number detection.
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PMID:Detection of submicroscopic constitutional chromosome aberrations in clinical diagnostics: a validation of the practical performance of different array platforms. 1828 35

Microarray-based comparative genomic hybridization (array CGH) is a fast and high-resolution approach to the diagnosis of a large number of genetic syndromes associated with loss or gain of the human genome. This technology has proven to be useful in several clinical settings, including postnatal diagnosis of mental retardation, developmental delay, and congenital malformation syndromes. We describe the use of array CGH for prenatal diagnosis of a range of chromosomal syndromes associated with congenital malformations visible by ultrasound. The procedure is reproducible in a clinical setting and provides reliable results in a short period (approximately 5 days). Thus, depending on the array used, array CGH may develop into an excellent tool for prenatal diagnosis.
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PMID:Prenatal diagnosis using array CGH. 1842 72

The deletion 9p syndrome is caused by a constitutional monosomy of part of the short arm of chromosome 9. It is clinically characterized by dysmorphic facial features (trigonocephaly, midface hypoplasia, and long philtrum), hypotonia and mental retardation. Deletion 9p is known to be heterogeneous and exhibits variable deletion sizes. The critical region for a consensus phenotype has been reported to be located within a approximately 4-6 Mb interval on 9p22. In the present study, deletion breakpoints were determined in 13 Dutch patients by applying fluorescence in situ hybridization (FISH) and in some specific cases by array-based comparative genomic hybridization (array CGH). No clear genotype-phenotype correlation could be established for various developmental features. However, we were able to narrow down the critical region for deletion 9p syndrome to approximately 300 kb. A functional candidate gene for trigonocephaly, the CER1 gene, appeared to be located just outside this region. Sequence analysis of this gene in nine additional patients with isolated trigonocephaly did not reveal any pathogenic mutations.
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PMID:Clinical and cytogenetic characterization of 13 Dutch patients with deletion 9p syndrome: Delineation of the critical region for a consensus phenotype. 1845 92

During a 6-year period, 590 patients suspected of having a minor or cryptic genomic imbalance as the cause of mental retardation with dysmorphic signs +/- malformations have been investigated with high-resolution comparative genomic hybridisation (HR-CGH) in our diagnostic laboratory. Thirty-six patients had a small chromosomal aberration detected by routine karyotyping, and 554 patients had a normal G-banded karyotype. In the latter group, a genomic imbalance was detected by HR-CGH in 40 patients (7.2%): 29 deletions, 3 duplications, 4 unbalanced translocations, and 4 occult trisomy mosaicisms. When microarray-based comparative genomic hybridisation (array-CGH) became available, all HR-CGH-positive samples were also investigated by 1 Mb resolution array-CGH for more precise mapping. From the 514 patients with normal HR-CGH findings, a subset of 20 patients with particularly high suspicion of having a chromosomal imbalance was selected for array-CGH. In four of them (20%), an imbalance was detected: three deletions and one duplication. Of note, 73 out of the 80 array-CGH mapped patients had a de novo chromosomal rearrangement (91%). Taken together, this work provides phenotype-genotype information on 80 patients with minor and cryptic chromosomal imbalances.
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PMID:Array-CGH fine mapping of minor and cryptic HR-CGH detected genomic imbalances in 80 out of 590 patients with abnormal development. 1846 Oct 90

Array comparative genomic hybridization (array CGH) has revolutionized the cytogenetic testing available for patients with learning disabilities who have "chromosomal" phenotypes with dysmorphic features and multiple anomalies. Screening large patient cohorts with mental retardation by array CGH has recently lead to the characterization of many novel microdeletion and microduplication syndromes, initially according to the shared cytogenetic aberrations, with secondary characterization of the corresponding phenotypes. This review provides a detailed clinical and molecular cytogenetic description of several of the most common of these aberrations. We have chosen to focus on patients in whom the cytogenetic abnormalities were principally described by array CGH, rather than by G-banded karyotyping or fluorescence in-situ hybridization. The syndromes that we have chosen include the 17q21.31 deletion and 17q21.31 duplication syndromes, 15q13.3 deletion syndrome, 16p11.2 deletion syndrome, 15q24 deletion syndrome, 1q41q42 deletion syndrome, 2p15p16.1 deletion syndrome and 9q22.3 deletion syndrome. In time, we hypothesize that at least some of these will become as clinically well characterized and recognizable to the clinician as the commoner microdeletion syndromes today. Although the full extent of the phenotypes is still evolving for many of these novel microdeletions, it is clear that array CGH has heralded an unparalleled era of discovery for clinical cytogenetics.
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PMID:Novel microdeletion syndromes detected by chromosome microarrays. 1851 78

OPHN1 mutations cause a syndromic form of mental retardation (MR) characterized by cerebellar hypoplasia, early hypotonia, motor and speech delay, with occasional seizures and strabismus. Here we report on a familial chromosome duplication spanning about 800 Kb of Xq12q13.1, associated with MR and a distinctive phenotype in the affected male, but not in his heterozygous mother. The parents were healthy and non-consanguineous with a history of three pregnancies. The first resulted in the birth of a boy with MR, motor impairment and seizures. The second pregnancy was terminated because of trisomy 18. At the time of the third, the first affected boy was analyzed by array-CGH, which revealed a 800 Kb duplication at Xq12q13.1, encompassing three genes, including OPHN1. This mutation was inherited from his healthy mother and was not present in any of the three maternal brothers. To our knowledge this is the first report of a clinical phenotype associated with duplication of Xq12q13.
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PMID:Association of syndromic mental retardation with an Xq12q13.1 duplication encompassing the oligophrenin 1 gene. 1851 29


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