+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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

Bmc Medical Genetics 18(1): 91

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. 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. 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.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 059337526

Download citation: RISBibTeXText

PMID: 28830375

DOI: 10.1186/s12881-017-0453-0

Related references

Exome analysis identified a novel missense mutation in the CLPP gene in a consanguineous Saudi family expanding the clinical spectrum of Perrault Syndrome type-3. Journal of the Neurological Sciences 353(1-2): 149-154, 2015

A novel homozygous variant of GPR98 causes usher syndrome type IIC in a consanguineous Chinese family by next generation sequencing. Bmc Medical Genetics 19(1): 99, 2018

Novel homozygous missense mutation in GAN associated with Charcot-Marie-Tooth disease type 2 in a large consanguineous family from Israel. Bmc Medical Genetics 17(1): 82, 2016

A novel homozygous PTH1R variant identified through whole-exome sequencing further expands the clinical spectrum of primary failure of tooth eruption in a consanguineous Saudi family. Archives of Oral Biology 67: 28-33, 2016

A Novel Missense Mutation in the CLPP Gene Causing Perrault Syndrome Type 3 in a Turkish Family. Journal of Clinical Research in Pediatric Endocrinology 8(4): 472-477, 2016

A Novel Homozygous Frameshift Variant in XYLT2 Causes Spondyloocular Syndrome in a Consanguineous Pakistani Family. Frontiers in Genetics 10: 144, 2019

A homozygous missense mutation in ERAL1, encoding a mitochondrial rRNA chaperone, causes Perrault syndrome. Human Molecular Genetics 26(13): 2541-2550, 2017

A MEI1 homozygous missense mutation associated with meiotic arrest in a consanguineous family. Human Reproduction 33(6): 1034-1037, 2018

Homozygous missense mutation in MED25 segregates with syndromic intellectual disability in a large consanguineous family. Journal of Medical Genetics 52(2): 123-127, 2015

Homozygous missense mutation in the LMAN2L gene segregates with intellectual disability in a large consanguineous Pakistani family. Journal of Medical Genetics 53(2): 138-144, 2016

Novel homozygous PANK2 mutation identified in a consanguineous Chinese pedigree with pantothenate kinase-associated neurodegeneration. Biomedical Reports 5(2): 217-220, 2016

A novel homozygous GALC variant has been associated with Krabbe disease in a consanguineous family. Neurological Sciences 39(12): 2123-2128, 2018

Novel biallelic missense mutations in CTC1 gene identified in a Chinese family with Coats plus syndrome. Journal of the Neurological Sciences 382: 142-145, 2017

Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome. American Journal of Human Genetics 87(2): 282-288, 2010

A novel missense NMNAT1 mutation identified in a consanguineous family with Leber congenital amaurosis by targeted next generation sequencing. Gene 569(1): 104-108, 2015