Clinical Exome Sequencing Identifies, Two Homozygous LOXHD1 Variants in Two Inbred Families With Pre-Lingual Hearing Loss From South India.

IF 1 4区 生物学 Q4 GENETICS & HEREDITY
Mathuravalli Krishnamoorthy, Chandru Jayasankaran, Sorna Lakshmi, Chodisetty Sarvani, Jeffrey Justin Margret, Subathra Mahalingam, Pavithra Amritkumar, Paridhy Vanniya Subramanyam, Sarrath Rathnaraajan S, C R Srikumari Srisailapathy
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引用次数: 0

Abstract

In recent years, numerous genetic variants have been linked with prelingual hearing loss (HL). Variants in the LOXHD1 gene (lipoxygenase homology domain-1) associated with DFNB77 are highly heterogeneous, with different auditory characteristics varying from stable to progressive and mild to profound. To date, 168 DFNB77 cases have been recorded worldwide. Forty-one hearing-impaired (HI) probands, who were previously excluded for a set of four common deafness-causing genes (viz., GJB2, GJB6, SLC26A4, and CDH23) from 33 HI families, were subjected to clinical exome sequencing (CES) involving 285 genes associated with HL. This was followed by a segregation analysis of the available members in the family. We identified two pathogenic LOXHD1 variants in two unrelated inbred families. One is a novel homozygous pathogenic nonsense variant (c.3999C > A; p.C1333X), whereas the other is a likely pathogenic missense variant (c.6046G > T; p.E2046K). In silico tools such as SIFT, PolyPhen-2, Mutation Taster, CADD, and REVEL scores were used to predict variant pathogenicity. Furthermore, American College of Medical Genetics and Genomics guidelines specific to HL were applied to finally classify a variant as pathogenic or otherwise. The frequency of LOXHD1 variants identified in our study is 4.88% (2/41). This is the first LOXHD1 report associated with non-syndromic HL in South Indian families.

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来源期刊
Annals of Human Genetics
Annals of Human Genetics 生物-遗传学
CiteScore
4.20
自引率
0.00%
发文量
34
审稿时长
3 months
期刊介绍: Annals of Human Genetics publishes material directly concerned with human genetics or the application of scientific principles and techniques to any aspect of human inheritance. Papers that describe work on other species that may be relevant to human genetics will also be considered. Mathematical models should include examples of application to data where possible. Authors are welcome to submit Supporting Information, such as data sets or additional figures or tables, that will not be published in the print edition of the journal, but which will be viewable via the online edition and stored on the website.
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