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Abstract
Background A substantial amount of nuclear genes have been identified to be implicated in genetic hearing loss, while X-linked hearing loss is genetically heterogeneous and relatively infrequent.
Objective To identify the causative gene mutation in a five-generation Chinese family with an X-linked recessive syndromic hearing loss (SHL).
Methods Targeted X-chromosome exome sequencing was conducted, and cosegregation analysis was performed in the members of the affected family. The in silico and expression studies were also performed.
Results A 2-bp missense mutation (c.1717_1718GC>AA, p.A573N) in the G protein-coupled receptor associated sorting protein 2 (GPRASP2) gene was identified in four hemizygous male patients and two heterozygous female carriers, which was cosegregated with the clinical phenotypes in this family. In silico analysis supported that this gene mutation is functionally deleterious, and it was detected that homologous Gprasp2 was highly expressed in multiple structures of the mouse cochlea, which suggested that GPRASP2 might be the genetic cause for the described disease phenotypes.
Conclusions This study presented a novel X-linked SHL combined with unique and unrecognised clinical features, and a missense variation of GPRASP2 was first identified to be implicated in X-linked SHL.
- Genetics
- Genetic screening/counselling
- Molecular genetics
- Clinical genetics
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Footnotes
GX and JY contributed equally.
Correction notice This article has been corrected since it published Online First. Non-syndromic hearing loss was incorrectly abbreviated to SHL, and SHL was not expanded in the first instance. Both these instances have been updated.
Contributors The first two authors (GX and JY) contributed equally to this work. GX, JY, QW, XQ and LW: performed the experiments. CL, XQ and YL: contributed reagents/materials/analysis tools. GX and JY: wrote the paper. XC: conception and design, revised the article.
Funding This research was supported by the grants from the National Natural Science Foundation of China (31171217, 31571302) and the Key Research and Development Program of Jiangsu Province (Social Development: BE2016762) to XC; the grants from Jiangsu Health Administration of China (LJ201120) and the Research Special Fund for Public Welfare Industry of Health, Ministry of Health of China (201202005) to GX.
Competing interests None declared.
Patient consent Obtained.
Ethics approval The Ethics Committee of Nanjing Medical University.
Provenance and peer review Not commissioned; externally peer reviewed.