Unknown

Dataset Information

0

Whole-exome sequencing of de novo genetic variants in a Chinese family with a sporadic case of congenital nonsyndromic hearing loss.


ABSTRACT: Background: We examined the genetic variants of a Chinese family with a 22-month-old infant with sporadic non-syndromic sensorineural hearing loss (NSHL). Methods: The whole-exome sequence data in the family, especially the de novo variants presented in the patient, were analyzed and the effect of the disease-causing genetic variants on the protein expression level and cellular localization were examined by cell-based functional assay. Results: The infant had no known NSHL-causing variants, except two compound heterozygous variants in connexin26 gene GJB2; one was the c.79G>A, c.341A>G haplotype from the asymptomatic mother who was benign, and the other was a de novo pathogenic c.262G>C (p.A88P). In vitro, GJB2 with c.262G>C was weakly expressed and displayed a punctate distribution in the cytoplasm and cytomembrane, while wild type GJB2 was robustly expressed in the cytomembrane. We deduced that the de novo pathogenic GJB2 c.262G>C exacerbated loss-of-function in the context of leaky variants c.79G>A, c.341A>G in the patient. Interestingly, further analysis of exome sequences revealed that the occurrence of de novo pathogenic variants in the infant was frequent. Among the total~47,000 variants, 143 were de novo in the patient, whereas among all 74 variants predicted to be pathogenic/likely pathogenic, 21 were heterozygous and two were homozygous de novo. The occurrence rate of de novo deleterious variants was much higher (31.1%, 23/74) than that in total (0.34%, 143/47,000). It is notable that most genes with de novo deleterious variants were environment-sensitive, such as GJB2, MNK1, MNK2, MUC4, RAD21 and DNA copy number variations. Conclusions: The full picture of genetic variants in the exome might help us to interpret the NSHL-causing variants. More research is needed into the causes of de novo deleterious variants and gene-environment interactions in congenital NSHL.

SUBMITTER: Hu S 

PROVIDER: S-EPMC8422347 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

altmetric image

Publications

Whole-exome sequencing of <i>de novo</i> genetic variants in a Chinese family with a sporadic case of congenital nonsyndromic hearing loss.

Hu Sijing S   Zhang Hao H   Liu Yunqiang Y   Liu Mohan M   Li Jingjing J   Liao Shunyao S  

F1000Research 20210202


<b>Background:</b> We examined the genetic variants of a Chinese family with a 22-month-old infant with sporadic non-syndromic sensorineural hearing loss (NSHL). <b>Methods:</b> The whole-exome sequence data in the family, especially the <i>de novo</i> variants presented in the patient, were analyzed and the effect of the disease-causing genetic variants on the protein expression level and cellular localization were examined by cell-based functional assay. <b>Results:</b> The infant had no known  ...[more]

Similar Datasets

| S-EPMC7434732 | biostudies-literature
| S-EPMC4499094 | biostudies-literature
| S-EPMC9578779 | biostudies-literature
| S-EPMC3709464 | biostudies-literature
| S-EPMC3046476 | biostudies-literature
| S-EPMC3115696 | biostudies-literature
| S-EPMC4775805 | biostudies-literature
| S-EPMC3955383 | biostudies-literature
| S-EPMC4360641 | biostudies-literature
| S-EPMC7839829 | biostudies-literature