title: Clinical,biochemical and molecular analysis of five Chinese patients with Sandhoff disease.
abstract: Sandhoff disease (SD) is a rare autosomal recessive lysosomal storage disorder of sphingolipid metabolism resulting from the deficiency of β-hexosaminidase (HEX). Mutations of the HEXB gene cause Sandhoff disease. In order to improve the diagnosis and expand the knowledge of the disease, we collected and analyzed relevant data of clinical diagnosis, biochemical investigation, and molecular mutational analysis in five Chinese patients with SD. The patients presented with heterogenous symptoms of neurologic deterioration. HEX activity in leukocytes was severely deficient. We identified seven different mutations, including three known mutations: IVS12-26G > A, p.T209I, p.I207V, and four novel mutations: p.P468PfsX62, p.L223P, p.Y463X, p.G549R. We also detected two different heterozygous mutations c.-122delC and c.-126C > T in the promoter which were suspected to be deleterious mutations. We attempted to correlate these mutations with the clinical presentation of the patients. Our study indicates that the mutation p.T209I and p.P468PfsX62 may link to the infantile form of SD. Our study expands the spectrum of genotype of SD in China, provides new insights into the molecular mechanism of SD and helps to the diagnosis and treatment of this disease.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Immunology and Rheumatology, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong, China.
authors.forename: Huasong
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, 9 Jinsui Road, Guangzhou, Guangdong, 510623, China. xxhuang321@163.com.
authors.forename: Yonglan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, 9 Jinsui Road, Guangzhou, Guangdong, 510623, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, 9 Jinsui Road, Guangzhou, Guangdong, 510623, China.
authors.forename: Jipeng
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, 9 Jinsui Road, Guangzhou, Guangdong, 510623, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, 9 Jinsui Road, Guangzhou, Guangdong, 510623, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Department of Radiology, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, 9 Jinsui Road, Guangzhou, Guangdong, 510623, China. liliuxia@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D011401:Promoter Regions, Genetic; D012497:Sandhoff Disease / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D063189:Symptom Assessment; D054821:beta-Hexosaminidase beta Chain / Q000235:genetics*
chemical_list: C513386:HEXB protein, human; D054821:beta-Hexosaminidase beta Chain
keywords: GM2 gangliosidosis; HEXB gene; Sandhoff disease; β-hexosaminidase