Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3

Item Type:	Article
Title:	Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3
Creators Name:	Kahrizi, K. and Hu, C.H. and Garshasbi, M. and Abedini, S.S. and Ghadami, S. and Kariminejad, R. and Ullmann, R. and Chen, W. and Ropers, H.H. and Kuss, A.W. and Najmabadi, H. and Tzschach, A.
Abstract:	As part of a large-scale, systematic effort to unravel the molecular causes of autosomal recessive mental retardation, we have previously described a novel syndrome consisting of mental retardation, coloboma, cataract and kyphosis (Kahrizi syndrome, OMIM 612713) and mapped the underlying gene to a 10.4-Mb interval near the centromere on chromosome 4. By combining array-based exon enrichment and next generation sequencing, we have now identified a homozygous frameshift mutation (c.203dupC; p.Phe69LeufsX2) in the gene for steroid 5α-reductase type 3 (SRD5A3) as the disease-causing change in this interval. Recent evidence indicates that this enzyme is required for the conversion of polyprenol to dolichol, a step that is essential for N-linked protein glycosylation. Independently, another group has recently observed SRD5A3 mutations in several families with a type 1 congenital disorder of glycosylation (CDG type Ix, OMIM 212067), mental retardation, cerebellar ataxia and eye disorders. Our results show that Kahrizi syndrome and this CDG Ix subtype are allelic disorders, and they illustrate the potential of next-generation sequencing strategies for the elucidation of single gene defects.
Keywords:	SRD5A3, Next Generation Sequencing, Congenital Disorder of Glycosylation, Mental Retardation, Autosomal Recessive, Consanguinity
Source:	European Journal of Human Genetics
ISSN:	1018-4813
Publisher:	Nature Publishing Group
Volume:	19
Number:	1
Page Range:	115-117
Date:	January 2011
Official Publication:	https://doi.org/10.1038/ejhg.2010.132
PubMed:	View item in PubMed

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