The conserved p.Arg108 residue in S1PR2 (DFNB68) is fundamental for proper hearing: evidence from a consanguineous Iranian family.
BMC Med Genet
; 19(1): 81, 2018 05 18.
Article
in En
| MEDLINE
| ID: mdl-29776397
ABSTRACT
BACKGROUND:
Genetic heterogeneity and consanguineous marriages make recessive inherited hearing loss in Iran the second most common genetic disorder. Only two reported pathogenic variants (c.323G>C, p.Arg108Pro and c.419A>G, p.Tyr140Cys) in the S1PR2 gene have previously been linked to autosomal recessive hearing loss (DFNB68) in two Pakistani families. We describe a segregating novel homozygous c.323G>A, p.Arg108Gln pathogenic variant in S1PR2 that was identified in four affected individuals from a consanguineous five generation Iranian family.METHODS:
Whole exome sequencing and bioinformatics analysis of 116 hearing loss-associated genes was performed in an affected individual from a five generation Iranian family. Segregation analysis and 3D protein modeling of the p.Arg108 exchange was performed.RESULTS:
The two Pakistani families previously identified with S1PR2 pathogenic variants presented profound hearing loss that is also observed in the affected Iranian individuals described in the current study. Interestingly, we confirmed mixed hearing loss in one affected individual. 3D protein modeling suggests that the p.Arg108 position plays a key role in ligand receptor interaction, which is disturbed by the p.Arg108Gln change.CONCLUSION:
In summary, we report the third overall mutation in S1PR2 and the first report outside the Pakistani population. Furthermore, we describe a novel variant that causes an amino acid exchange (p.Arg108Gln) in the same amino acid residue as one of the previously reported Pakistani families (p.Arg108Pro). This finding emphasizes the importance of the p.Arg108 amino acid in normal hearing and confirms and consolidates the role of S1PR2 in autosomal recessive hearing loss.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arginine
/
Amino Acid Substitution
/
Receptors, Lysosphingolipid
/
Hearing Loss
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Female
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
BMC Med Genet
Journal subject:
GENETICA MEDICA
Year:
2018
Document type:
Article
Affiliation country: