Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
J Hum Genet. 2010 Mar;55(3):142-6. doi: 10.1038/jhg.2009.141. Epub 2010 Jan 29.
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.
Marinesco-Sjögren 综合征（MSS）是一种罕见的常染色体隐性疾病。SIL1 基因的突变占大多数 MSS 病例的原因。然而，已经报道了一些具有典型 MSS 但没有 SIL1 突变的个体。在这项研究中，我们在一个具有 MSS 的日本家系中鉴定出两个新的突变，其中一个是使用 PCR 直接测序方案未检测到的基因内缺失。这个家庭由三个受影响的兄弟姐妹、一个未受影响的兄弟姐妹和未受影响的父母组成。我们通过 PCR 发现所有受影响的兄弟姐妹的第 6 外显子中存在 5 个碱基的缺失，del598-602（GAAGA）。因此，我们预计父母双方都是该突变的杂合子。正如预期的那样，父亲是杂合子，而母亲没有突变。然后我们进行了比较基因组杂交和定量 PCR 分析，并在患者和母亲的第 6 外显子中发现了大约 58kb 的缺失。结果，母亲是 58kb 缺失的半合子。受影响的兄弟姐妹包含两个突变，一个 5bp 和一个 58kb 的缺失，导致 SIL1 基因功能障碍。一些报道的没有 SIL1 基因碱基改变的 MSS 病例可能是由于缺失而不是基因座异质性引起的。
