title: Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjögren syndrome.
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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. takahata@nagasaki-u.ac.jp
authors.forename: Taichi
authors.initials: T
authors.lastname: Takahata
authors.forename: Koki
authors.initials: K
authors.lastname: Yamada
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamada
authors.forename: Shinji
authors.initials: S
authors.lastname: Ono
authors.forename: Akira
authors.initials: A
authors.lastname: Kinoshita
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Matsuzaka
authors.forename: Koh-ichiro
authors.initials: K
authors.lastname: Yoshiura
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitaoka
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D013132:Spinocerebellar Degenerations / Q000235:genetics*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C418483:SIL1 protein, human