Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjogren syndrome

作者：Takahata Taichi^*; Yamada Koki; Yamada Yoshihisa; Ono Shinji; Kinoshita Akira; Matsuzaka Tetsuo; Yoshiura Koh ichiro; Kitaoka Takashi

来源：Journal of Human Genetics, 2010, 55(3): 142-146.

DOI：10.1038/jhg.2009.141

• array CGH
• Marinesco-Sjogren syndrome
• quantitative PCR
• SIL1 gene

Marinesco-Sjogren syndrome (MSS) is a rare autosomal recessive disorder. Mutation in the SIL1 gene accounts for the majority of MSS cases. However, some individuals with typical MSS without SIL1 mutations have been reported. In this study, we identified two novel mutations in a Japanese pedigree with MSS, one of which was an intragenic deletion not detected using the PCR-direct sequencing protocol. This family consisted of three affected siblings, an unaffected sibling and unaffected parents. We found a homozygous 5-bp deletion, del598-602(GAAGA), in exon 6 of all affected siblings by PCR. Thus, we expected that both parents would be heterozygous for the mutation. As expected, the father was heterozygous, whereas the mother demonstrated no mutations. We then carried out array comparative genomic hybridization and quantitative PCR analyses, and identified an approximately 58 kb deletion in exon 6 in the patients and mother. As a result, the mother was hemizygous for a 58-kb deletion. The affected siblings contained two mutations, a 5-bp and a 58-kb deletion, resulting in SIL1 gene dysfunction. It is possible that some reported cases of MSS without base alterations in the SIL1 gene are caused by deletions rather than locus heterogeneity. Journal of Human Genetics (2010) 55, 142-146; doi: 10.1038/jhg.2009.141; published online 29 January 2010

• 出版日期2010-3