Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cornelia de Lange syndrome (CdLS; OMIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by distinctive dysmorphic facial features, severe growth and developmental delay and abnormalities of the upper limbs. About 50% of CdLS patients have been found to have heterozygous mutations in the NIPBL gene and a few cases were recently found to be caused by mutations in the X-linked SMC1L1 gene. We performed a mutation screening of all NIPBL coding exons by direct sequencing in 11 patients (nine sporadic and two familial cases) diagnosed with CdLS in Sweden and detected mutations in seven of the cases. All were de novo, and six of the mutations have not been previously described. Four patients without identifiable NIPBL mutations were subsequently subjected to multiplex ligation-dependent probe amplification analysis to exclude whole exon deletions/duplications of NIPBL. In addition, mutation analysis of the 5' untranslated region (5' UTR) of NIPBL was performed. Tiling resolution array comparative genomic hybridization analysis was carried out on these four patients to detect cryptic chromosome imbalances and in addition the boys were screened for SMC1L1 mutations. We found a de novo 9p duplication with a size of 0.6 Mb in one of the patients with a CdLS-like phenotype but no mutations were detected in SMC1L1. So far, two genes (NIPBL and SMC1L1) have been identified causing CdLS or CdLS-like phenotypes. However, in a considerable proportion of individuals demonstrating the CdLS phenotype, mutations in any of these two genes are not found and other potential loci harboring additional CdLS-causing genes should be considered.
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PMID:Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients. 1710 45

Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder characterized by facial dysmorphism, growth and mental retardation, microcephaly, and various malformations. Heterozygous mutations in the NIPBL gene have been detected in approximately 45% of affected individuals. Recently, a second CdLS gene, mapping to the X chromosome, has been identified: SMC1L1 (structural maintenance of chromosomes 1-like 1; or SMC1A). In order to estimate the incidence and refine the clinical presentation of X-linked CdLS, we have screened a series of 11 CdLS boys carrying no NIPBL anomaly. We have identified two novel de novo SMC1L1 missense mutations (c.587G>A [p.Arg196His] and c.3254A>G [p.Tyr1085Cys]). Our results confirm that SMC1L1 mutations cause CdLS and support the view that SMC1L1 accounts for a significant fraction of boys with unexplained CdLS. Furthermore, we suggest that SMC1L1 mutations have milder effects than NIPBL mutations with respect to pre- and postnatal growth retardation and associated malformations. If confirmed, these data may have important implications for directing mutation screening in CdLS.
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PMID:Incidence and clinical features of X-linked Cornelia de Lange syndrome due to SMC1L1 mutations. 1722 63

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

Cornelia de Lange syndrome (CdLS) is a rare, multiple congenital anomaly/mental retardation syndrome characterized by clinical variability and caused by mutations in the NIPBL (50-60%), SMC1L1 and SMC3 genes (5%), which encode for proteins involved in sister chromatid cohesion. Almost all of the studies of premature chromatid separation (PCS) in CdLS patients have failed to demonstrate that it is specific to CdLS, thus making its diagnostic use controversial. In order to verify the diagnostic usefulness of PCS screening in CdLS, we analysed metaphase spreads from 29 CdLS patients and 24 controls using a rigorous protocol to induce PCS, and precise criteria to score the affected chromosomes. Following exclusion of significant intra-sample variation we scored under blind conditions 150 spreads from a single preparation of each case and computed the ratio between the number of prematurely separated chromatids and the total number of chromatids. The results indicate the extreme variability of PCS in both cohorts (CdLS: mean 2.8 +/- 2.8%; controls: mean 4.0 +/- 5.4%) and highlight the difficulty of PCS monitoring, especially when selecting the control population. The absence of any difference in the frequency of PCS between the patients and controls, or between patients with different clinical or genetic backgrounds, precludes its potential use as an additional diagnostic tool.
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PMID:Premature chromatid separation is not a useful diagnostic marker for Cornelia de Lange syndrome. 1969 Sep 71