Novel Mutations in SIL1 Gene in a Japanese Pedigree With Marinesco-Sjögren Syndrome

Abstract

Purpose: : Marinesco-Sjögren Syndrome (MSS; OMIM 248800) is a rare autosomal recessive disorder characterized by congenital cataracts, cerebellar ataxia, myopathy, and mental retardation. In 2005, two groups independently identified several mutations in SIL1 gene with typical MSS. However, only a few mutations in SIL1 gene reported subsequently. The purpose of this study was to identify mutations in a Japanese pedigree with MSS.

Methods: : The object family with MSS consisted of three affected siblings, an unaffected sibling and their unaffected parents. All the affected individuals were born after normal pregnancy and delivery to non-consanguineous parents. All samples were collected after obtaining written informed consent, and the study protocol was approved the Committee for the Ethical Issues on Human Genome and Gene Analysis in Nagasaki University. All 10 exons of SIL1 gene in all family members were screened for mutations by polymerase chain reaction (PCR) and direct sequencing. Real-time quantitative PCR was used to determine the copy number of SIL1 gene.

Results: : We firstly sequenced all 10 exons of SIL1 gene in four siblings, and identified a homozygous del598-602(GAAGA) mutation in exon 6 in the electropherograms in all three affected siblings. No mutations were found in an unaffected sibling. Therefore we expected that the affected siblings were homozygous for the mutation because of descendant from a founder, and both parents should have been heterozygous for the mutation. As expected, we found that the father is a heterozygous of del598-602(GAAGA) mutation. However, no mutations were found in all 10 exons of SIL1 gene in the mother unexpectedly. The mutation analyses suggested that the mother might be a hemizygous at least around exon 6. We carried out quantitative PCR analyses in all family members and determined the copy number of exon 6 in SIL1 gene. The results indicated that the unaffected sibling and the father had two copies, and the three affected siblings and the mother had one copy.

Conclusions: : We identified that the father was heterozygous for the del598-602(GAAGA) in SIL1 gene, the mother was hemizygous for SIL1 gene including exon 6, and the three affected siblings were compound heterozygous for the del598-602(GAAGA) and deletion of SIL1 gene including exon 6.

Keywords: genetics • cataract • gene/expression