A homozygous missense variant in HSD17B4 identified in a consanguineous Chinese Han family with type II Perrault syndrome.
A homozygous missense variant in HSD17B4 identified in a consanguineous Chinese Han family with type II Perrault syndrome.
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中国汉族 II 型 Perrault 综合征近亲家族中发现 HSD17B4 纯合错义变异
DOI：
10.1186/s12881-017-0453-0
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发表时间：
2017-08-23
影响因子：
--
通讯作者：
Sun YM
中科院分区：
文献类型：
--
作者：
Chen K;Yang K;Luo SS;Chen C;Wang Y;Wang YX;Li DK;Yang YJ;Tang YL;Liu FT;Wang J;Wu JJ;Sun YM
背景：Perrault综合征是一种罕见的多系统疾病，表现为感音神经性听力损失，女性原发性卵巢功能不全和神经系统特征。该综合征是异质性的遗传和表型。病例介绍：我们报告了一个近亲家庭（两个受影响的姐妹篇）与佩罗综合征。先证者具有Perrault综合征的特征：卵巢发育不全，双侧听力下降，神经系统体征明显。采用靶基因测序和三重重复引物PCR（TP-PCR）结合毛细管电泳检测先证者的致病突变。通过桑格测序，在先证者中进一步证实了检测到的变异，并在其他家族成员中进行了检测。先证者和她的姐姐都被发现是新变异HSD 17 B4 c.298G > T（p.A100S）纯合子，而他们的父母是杂合子。结论：本研究结果支持HSD 17 B4基因是Perrault综合征的致病基因之一，可能的致病变异体为c.298G > T（p.A100S）。在由HSD 17 B4突变引起的病例中发现了小脑损害的特殊表现。同时应注意与D-双功能蛋白缺乏症和遗传性共济失调相鉴别。
Background:Perrault 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 presentation:We 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.Conclusions:Our 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.
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影响因子：
0.2
作者：
Geethalakshmi, Sampathkumar;Narendrakumar, Veerasigamani
通讯作者：
Narendrakumar, Veerasigamani
影响因子：
9.8
作者：
Jenkinson, Emma M.;Rehman, Atteeq U.;Newman, William G.
通讯作者：
Newman, William G.
影响因子：
9.8
作者：
van Grunsven, EG;van Berkel, E;Wanders, RJA
通讯作者：
Wanders, RJA
影响因子：
2
作者：
Gronborg, Sabine;Kraetzner, Ralph;Gaertner, Jutta
通讯作者：
Gaertner, Jutta
影响因子：
1.8
作者：
Kim, Min Jeong;Kim, Sa Jin;Kim, Yonggoo
通讯作者：
Kim, Yonggoo