A novel splicing mutation of TIMM8A causes X-linked congenital sensorineural deafness and dystonia syndrome in a Chinese family
The deafness-dystonia syndrome (DDS) is also known as Mohr-Tranebjaerg syndrome (MTS, MIM 304700). It is a rare X-linked recessive neurological disorder involving in progressive dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness except progressive sensorineural deafness. This disease was resulting from loss-of-function mutations in the nuclear TIMM8A gene that involved in the transport and sorting of proteins to the mitochondrial inner membrane. Up to now, twelve different mutations (including seven premature stops, three altered splicing and two missense mutations) in TIMMSA had been reported in individuals with DDS.In this study, a three-generation Chinese family, including four patients and thirteen normal individuals, from Hubei Provience with X-linked recessive congenital sensorineural deafness and dystonia have identified and characterized. The proband showed dysarthria and spastic gait excep1 sensorineural deafness and dystonia. Linkage was identified with marker DXS1106. Haplotype analysis defined the causative gene between DXS986 and DXS8055. The TIMM8A and PRPS1 genes are closely linked to the disease of this family. Mutational analysis of all exons and exon-intron boundaries of TIMM8A and PRPS1 genes was carried out using direct DNA sequence analysis. A novel splicing mutation IVSl-2delA of the TIMMSA is found in proband. This was found the fourth splicing mutation. All male patients in the family were hemizygous for the mutation; the female carriers were heterozygous for the mutation. But the PRPS1 gene was normal.
X-linked congenital sensorineural deafness and dystonia syndrome Linkage analysis Mutation detection T1MM8A RT-PCR
Cheng Wang Yulei Li Jun YuLuo Jing Yu Liu
College of Life Science and Technology. Huazhong University of Science and Technology, Wuhan, Hubei, Affiliated Secondary School, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, P.
国内会议
乌鲁木齐
英文
93
2011-07-01（万方平台首次上网日期，不代表论文的发表时间）