A homozygous missense variant in HSD17B4 identified in a consanguineous Chinese Han family with type II Perrault syndrome

BMC Medical Genetics

Case Report

Su-Shan Luo¹  Yu-Jie Yang¹  Ke Yang¹  Yi-Xuan Wang¹  Jian Wang¹  Yi-Min Sun¹  Chen Chen¹  Feng-Tao Liu¹  Ying Wang¹  Da-Ke Li¹  Jian-Jun Wu¹  Kui Chen¹  Yi-Lin Tang¹ 

[1] Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, 200040, Shanghai, China;

关键词: Perrault syndrome;    HSD17B4;    Variant;    Neurological features;    Ovarian dysgenesis;    Sensorineural deafness;   

DOI  :  10.1186/s12881-017-0453-0

 received in 2016-11-15, accepted in 2017-08-14,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundPerrault syndrome is a rare multisystem disorder that manifests with sensorineural hearing loss in both sexes, primary ovarian insufficiency in females and neurological features. The syndrome is heterogeneous both genetically and phenotypically.Case presentationWe reported a consanguineous family (two affected sisters) with Perrault syndrome. The proband had the characteristics of Perrault syndrome: ovarian dysgenesis, bilateral hearing loss and obvious neurological signs. Target genetic sequencing and triplet repeat primed PCR (TP-PCR) plus capillary electrophoresis was conducted to detect causative mutations in the proband. The detected variant was further confirmed in the proband and tested in other family members by Sanger sequencing. Both the proband and her sister were found homozygous for the novel variant HSD17B4 c.298G > T (p.A100S) with their parents heterozygous. Detected by western blot, the protein expression of HSD17B4 mutant was much lower than that of the wild type in SH-SY5Y cells transfected by HSD17B4 wild type or mutant plasmid, which indicated the pathogenicity of the HSD17B4 mutation.ConclusionsOur findings supported that HSD17B4 was one of the genes contributing to Perrault syndrome with the likely pathogenic variant c.298G > T (p.A100S). Special manifestations of cerebellar impairment were found in cases caused by HSD17B4 mutations. Besides, attention should be paid to distinguish Perrault syndrome from D-bifunctional protein deficiency and hereditary ataxia.

【 授权许可】

CC BY   
© The Author(s). 2017