Goto Masahide, Okada Mari, Komaki Hirofumi, Sugai Kenji, Sasaki Masayuki, Noguchi Satoru, Nonaka Ikuya, Nishino Ichizo, Hayashi Yukiko K
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Orphanet J Rare Dis. 2014 Apr 23;9:58. doi: 10.1186/1750-1172-9-58.
Marinesco-Sjögren syndrome (MSS) is an autosomal recessive multisystem disorder characterized by the tetralogy of cerebellar ataxia, congenital cataracts, intellectual disability, and progressive muscle weakness due to myopathy. MSS is extremely rare, and its clinical, pathological, and genetic features are not yet fully understood.
We conducted a nationwide, questionnaire-based survey on MSS in Japan and carefully reviewed the medical records of 36 patients suspected of having this disease. In addition, pathological examinations of muscles, sequence and haplotype analysis in SIL1 were performed.
The patients had been examined between the ages of 2 and 52 years. Delayed psychomotor development and cataracts from early childhood were observed in all patients, whereas no life-threatening events were observed. Mutations in SIL1 were identified in 24 of the 27 patients tested, and 43 of the 48 chromosomes possessed the SIL1 c.936dupG (p.Leu313fs) mutation. The haplotype analysis revealed that 31 of the 32 chromosomes (96.9%) with the c.936dupG mutation had the same haplotype.
The results of haplotype analysis suggested the presence of a founder effect. The clinical features of patients without SIL1 mutations were indistinguishable from those with SIL1 mutations, suggesting the genetic heterogeneity of MSS.
马里内斯科 - 舍格伦综合征（MSS）是一种常染色体隐性遗传的多系统疾病，其特征为小脑共济失调、先天性白内障、智力残疾以及因肌病导致的进行性肌无力四联征。MSS极为罕见，其临床、病理及遗传特征尚未完全明确。
我们在日本开展了一项基于问卷的全国性MSS调查，并仔细查阅了36例疑似患有该疾病患者的病历。此外，还对肌肉进行了病理检查，对SIL1进行了序列和单倍型分析。
患者接受检查的年龄在2岁至52岁之间。所有患者均观察到幼儿期精神运动发育迟缓及白内障，未观察到危及生命的事件。在27例接受检测的患者中，有24例鉴定出SIL1突变，48条染色体中有43条携带SIL1 c.936dupG（p.Leu313fs）突变。单倍型分析显示，携带c.936dupG突变的32条染色体中有31条（96.9%）具有相同的单倍型。
单倍型分析结果提示存在奠基者效应。无SIL1突变患者的临床特征与有SIL1突变患者无法区分，提示MSS存在遗传异质性。
