Novel SIL1 nonstop mutation in a Chinese consanguineous family with Marinesco-Sjögren syndrome and Dandy-Walker syndrome.
Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive disorder, which is characterized by congenital cataracts, cerebellar ataxia, progressive muscle weakness, and delayed psychomotor development. SIL1, which is located at 5q31.2, is the only gene known to cause MSS. Dandy-Walker syndrome (DWS) is defined by hypoplasia, upward rotation of the cerebellar vermis, and cystic dilation of the fourth ventricle; however, its genetic pathogeny remains unclear. Here, we report a Chinese consanguineous family with MSS and DWS. Whole exome sequencing identified a novel nonstop mutation in SIL1. Sanger sequencing revealed that the mutation was segregated in this family according to a recessive mode of inheritance. We found that the mutation changed a stop codon (TGA) to an arginine codon (CGA), and no in-frame termination codon in the 3' untranslated region (UTR) of SIL1 could be found. The mRNA levels of SIL1 were decreased by 56.6% and 37.5% in immortalized lymphoblasts of the patients respectively; the protein levels of SIL1 were substantially decreased. This case study is the first report on Chinese MSS patients, MSS complicated by DWS, and a nonstop mutation in SIL1. Our findings imply the pathogenetic association between DWS and MSS.
State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
Nan
N
Gai
State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
Chen
C
Jiang
State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
Yong-Yi
YY
Zou
State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
Yu
Y
Zheng
State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China; Hunan Jiahui Genetics Hospital, 110 Xiangya Road, Changsha, Hunan 410078, China. Electronic address: liangdesheng@sklmg.edu.cn.
De-Sheng
DS
Liang
State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China; Hunan Jiahui Genetics Hospital, 110 Xiangya Road, Changsha, Hunan 410078, China. Electronic address: wulingqian@sklmg.edu.cn.
Ling-Qian
LQ
Wu
D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D002648:Child; D002681:China; D003241:Consanguinity; D003616:Dandy-Walker Syndrome / Q000150:complications* / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D013132:Spinocerebellar Degenerations / Q000150:complications* / Q000235:genetics*
D020662:Guanine Nucleotide Exchange Factors; C418483:SIL1 protein, human
Dandy-Walker syndrome; Marinesco-Sjögren syndrome; Nonstop mutation; SIL1