Abstract
Marinesco–Sjögren 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.
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Acknowledgements
K Yamada was supported partly by a Grants-in-Aid for Scientific Research Category, no. 18791284 from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT). K Yoshiura was supported partly by a Grant-in-Aid for Scientific Research from the Ministry of Health, Labour and Welfare, and partly by grants from the Takeda Scientific Foundation and the Naito Foundation. We are greatly indebted to all the participants of this research. We also thank Ms M Ooga and C Hayashida for their excellent technical assistance.
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Takahata, T., Yamada, K., Yamada, Y. et al. Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco–Sjögren syndrome. J Hum Genet 55, 142–146 (2010). https://doi.org/10.1038/jhg.2009.141
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DOI: https://doi.org/10.1038/jhg.2009.141
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