Cataracts, ataxia, short stature, and mental retardation in a Chinese family mapped to Xpter-q13.1.
Six males in a Chinese family affected by congenital cataracts, cerebellar ataxia, short stature, and mental retardation, which were tentatively named CASM syndrome. Eight female carriers in the family had cataracts alone. Linkage analysis demonstrated that the disease is transmitted through X-linked inheritance, either by setting the syndrome in males as an X-linked recessive trait, or by setting cataracts in the family as an X-linked dominant trait. The gene responsible for the syndrome is mapped to Xpter-Xq13.1, with the highest lod score of 3.91 for DXS1226, DXS991, and DXS1213 at theta = 0. Haplotype analysis identified that the allele harboring the disease gene co-segregated with all female carriers as well as affected males in the family. Clinically and genetically, the disease in this family is different from any known disease. Major features of CASM syndrome that distinguish it from other diseases are X-linked inheritance and cataracts in carrier females.
Guo
Xiangming
X
Key Laboratory of Ophthalmology of the Ministry of Education and Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
Shen
Huangxuan
H
Key Laboratory of Ophthalmology of the Ministry of Education and Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
Xiao
Xueshan
X
Key Laboratory of Ophthalmology of the Ministry of Education and Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
Dai
Qilin
Q
Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Li
Shiqiang
S
Key Laboratory of Ophthalmology of the Ministry of Education and Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
Jia
Xiaoyun
X
Key Laboratory of Ophthalmology of the Ministry of Education and Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
Hejtmancik
J Fielding
JF
Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Zhang
Qingjiong
Q
Key Laboratory of Ophthalmology of the Ministry of Education and Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China. qingjiongzhang@yahoo.com.|Department of Ophthalmic Genetics and Molecular Biology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie Road, Guangzhou, 510060, China. qingjiongzhang@yahoo.com.
D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001259:Ataxia / Q000235:genetics*; D002386:Cataract / Q000235:genetics*; D002648:Child; D002681:China; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006130:Growth Disorders / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype