Homozygous mutations in Pakistani consanguineous families with prelingual nonsyndromic hearing loss

• DOI: 10.1007/s11033-020-06037-7
• Publication Date: 2020-12-02T18:02:46Z
• Authors: Hye Ri Park; Sumaira Kanwal; Si On Lim; Da Eun Nam; Yu Jin Choi; Ki Wha Chung
• Keywords: Adult; Male; 0301 basic medicine; Adolescent; Hearing Loss, Sensorineural; Calcium-Binding Proteins; Homozygote; Mutation, Missense; Cadherin Related Proteins; Membrane Proteins; Deafness; Cadherins; 3. Good health; Consanguinity; 03 medical and health sciences; Receptors, Estrogen; Child, Preschool; Humans; Female; Pakistan; Child

Autosomal recessive nonsyndromic hearing loss (DFNB) is relatively frequent in Pakistan, which is thought to be mainly due to relatively frequent consanguinity. DFNB genes vary widely in their kinds and functions making molecular diagnosis difficult. This study determined the genetic causes in five Pakistani DFNB families with prelingual onset. The familial genetic analysis identified four pathogenic or likely pathogenic homozygous mutations by whole exome sequencing: two splicing donor site mutations of c.787+1G>A in ESRRB (DFNB35) and c.637+1G>T in CABP2 (DFNB93) and two missense mutations of c.7814A>G (p.Asn2605Ser) in CDH23 (DFNB12) and c.242G>A (p.Arg81His) in TMIE (DFNB6). The ESRRB and TMIE mutations were novel, and the TMIE mutation was observed in two families. The two missense mutations were located at well conserved sites and in silico analysis predicted their pathogenicity. This study identified four homozygous mutations as the underlying cause of DFNB including two novel mutations. This study will be helpful for the exact molecular diagnosis and treatment of deafness patients.