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)

Structural variation (copy number variation [CNV] including deletion and duplication, translocation, inversion) of chromosomes has been identified in some individuals with autism spectrum disorder (ASD), but the full etiologic role is unknown. We performed genome-wide assessment for structural abnormalities in 427 unrelated ASD cases via single-nucleotide polymorphism microarrays and karyotyping. With microarrays, we discovered 277 unbalanced CNVs in 44% of ASD families not present in 500 controls (and re-examined in another 1152 controls). Karyotyping detected additional balanced changes. Although most variants were inherited, we found a total of 27 cases with de novo alterations, and in three (11%) of these individuals, two or more new variants were observed. De novo CNVs were found in approximately 7% and approximately 2% of idiopathic families having one child, or two or more ASD siblings, respectively. We also detected 13 loci with recurrent/overlapping CNV in unrelated cases, and at these sites, deletions and duplications affecting the same gene(s) in different individuals and sometimes in asymptomatic carriers were also found. Notwithstanding complexities, our results further implicate the SHANK3-NLGN4-NRXN1 postsynaptic density genes and also identify novel loci at DPP6-DPP10-PCDH9 (synapse complex), ANKRD11, DPYD, PTCHD1, 15q24, among others, for a role in ASD susceptibility. Our most compelling result discovered CNV at 16p11.2 (p = 0.002) (with characteristics of a genomic disorder) at approximately 1% frequency. Some of the ASD regions were also common to mental retardation loci. Structural variants were found in sufficiently high frequency influencing ASD to suggest that cytogenetic and microarray analyses be considered in routine clinical workup.
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PMID:Structural variation of chromosomes in autism spectrum disorder. 1825 27

Mendelian disorders of the epigenetic machinery (MDEMs), also named chromatin modifying disorders, are a broad group of neurodevelopmental disorders, caused by mutations in functionally related chromatin genes. Mental retardation autosomal dominant 23 (MRD23) syndrome, due to SETD5 gene mutations, falls into this group of disorders. KBG syndrome, caused by ANKRD11 gene haploinsufficiency, is a chromatin related syndrome not formally belonging to this category. We performed high resolution array CGH and trio-based WES on three molecularly unsolved patients with an initial KBGS clinical diagnosis. A de novo deletion of 116 kb partially involving SETD5 and two de novo frameshift variants in SETD5 were identified in the patients. The clinical re-evaluation of the patients was consistent with the molecular findings, though still compatible with KBGS due to overlapping phenotypic features of KBGS and MRD23. Careful detailed expert phenotyping ascertained some facial and physical features that were consistent with MRD23 rather than KBGS. Our results provide further examples that loss-of-function pathogenic variants in genes encoding factors shaping the epigenetic landscape, lead to a wide phenotypic range with significant clinical overlap. We recommend that clinicians consider SETD5 gene haploinsufficiency in the differential diagnosis of KBGS. Due to overlap of clinical features, careful and detailed phenotyping is important and a large gene panel approach is recommended in the diagnostic workup of patients with a clinical suspicion of KBGS.
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PMID:SETD5 Gene Haploinsufficiency in Three Patients With Suspected KBG Syndrome. 3279 91