Open AccessNext generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3
Author(s) -
Kimia Kahrizi,
Cougar Hao Hu,
Masoud Garshasbi,
Seyedeh Sedigheh Abedini,
Shirin Ghadami,
Ariana Kariminejad,
Reinhard Ullmann,
Wei Chen,
HansHilger Ropers,
Andreas W. Kuß,
Hossein Najmabadi,
Andreas Tzschach
Publication year - 2010
Publication title -
european journal of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.587
H-Index - 125
eISSN - 1476-5438
pISSN - 1018-4813
DOI - 10.1038/ejhg.2010.132
Subject(s) - frameshift mutation , genetics , biology , exon , mutation , gene
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.