Dataset Information

Whole-exome sequencing identified compound heterozygous variants in ROR2 gene in a fetus with Robinow syndrome.

ABSTRACT: BACKGROUND:Autosomal recessive Robinow syndrome (ARRS) is a rare genetic disorder, which affects the development of multiple systems, particularly the bones. OBJECTIVES:The aim of this study was to investigate the genetic cause of a ARRS fetus and to evaluate the reliability of whole-exome sequencing (WES) in prenatal diagnosis on cases with indistinguishable multiple malformation. METHODS:Clinical and ultrasonic evaluations were conducted on the fetus, and multiplatform genetic techniques were used to identify the variation responsible for RS. The pathogenicity of the novel variation was evaluated by in silico methods. Western blotting (WB) and immunohistochemistry (IHC) were performed on fetal tissues after the fetus' stillbirth and postabortal autopsy. RESULTS:A compound heterozygous variation consisting c.613C > T and c.904C > T in ROR2 gene was identified. In silico prediction suggested that c.904C > T was a deleterious variant. IHC result demonstrated that ror2 expression level of the proband in osteochondral tissue significantly increased comparing with that of the control sample. CONCLUSIONS:For the first time in Chinese population, we characterized a novel variation in ROR2 gene causing ARRS. This study extended the mutation spectrum of ARRS and provided a promising strategy for prenatal diagnosis of cases with ambiguous multiple deformities.

SUBMITTER: Yang K

PROVIDER: S-EPMC7031599 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Whole-exome sequencing identified compound heterozygous variants in ROR2 gene in a fetus with Robinow syndrome.

Yang Kai K Zhu Jianjiang J Tan Ya Y Sun Xiaofei X Zhao Huawei H Tang Guodong G Zhang Dongliang D Qi Hong H

Journal of clinical laboratory analysis 20191016 2

<h4>Background</h4>Autosomal recessive Robinow syndrome (ARRS) is a rare genetic disorder, which affects the development of multiple systems, particularly the bones.<h4>Objectives</h4>The aim of this study was to investigate the genetic cause of a ARRS fetus and to evaluate the reliability of whole-exome sequencing (WES) in prenatal diagnosis on cases with indistinguishable multiple malformation.<h4>Methods</h4>Clinical and ultrasonic evaluations were conducted on the fetus, and multiplatform ge ...[more]

PMID: 31617258

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Project description:BackgroundMany hearing-loss diseases are demonstrated to have Mendelian inheritance caused by mutations in single gene. However, many deaf individuals have diseases that remain genetically unexplained. Auditory neuropathy is a sensorineural deafness in which sounds are able to be transferred into the inner ear normally but the transmission of the signals from inner ear to auditory nerve and brain is injured, also known as auditory neuropathy spectrum disorder (ANSD). The pathogenic mutations of the genes responsible for the Chinese ANSD population remain poorly understood.MethodsA total of 127 patients with non-syndromic hearing loss (NSHL) were enrolled in Guangxi Zhuang Autonomous Region. A hereditary deafness gene mutation screening was performed to identify the mutation sites in four deafness-related genes (GJB2, GJB3, 12S rRNA, and SLC26A4). In addition, whole-exome sequencing (WES) was applied to explore unappreciated mutation sites in the cases with the singularity of its phenotype.ResultsWell-characterized mutations were found in only 8.7% (11/127) of the patients. Interestingly, two mutations in the OTOF gene were identified in two affected siblings with ANSD from a Chinese family, including one nonsense mutation c.1273C > T (p.R425X) and one missense mutation c.4994 T > C (p.L1665P). Furthermore, we employed Sanger sequencing to confirm the mutations in each subject. Two compound heterozygous mutations in the OTOF gene were observed in the two affected siblings, whereas the two parents and unaffected sister were heterozygous carriers of c.1273C > T (father and sister) and c.4994 T > C (mother). The nonsense mutation p.R425X, contributes to a premature stop codon, may result in a truncated polypeptide, which strongly suggests its pathogenicity for ANSD. The missense mutation p.L1665P results in a single amino acid substitution in a highly conserved region.ConclusionsTwo mutations in the OTOF gene in the Chinese deaf population were recognized for the first time. These findings not only extend the OTOF gene mutation spectrum for ANSD but also indicate that whole-exome sequencing is an effective approach to clarify the genetic characteristics in non-syndromic ANSD patients.

Dataset Information

Whole-exome sequencing identified compound heterozygous variants in ROR2 gene in a fetus with Robinow syndrome.

Publications

Whole-exome sequencing identified compound heterozygous variants in ROR2 gene in a fetus with Robinow syndrome.

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