title: Novel mutations confirm that COL11A2 is responsible for autosomal recessive non-syndromic hearing loss DFNB53.
abstract: Hearing loss (HL) is a major public health issue. It is clinically and genetically heterogeneous.The identification of the causal mutation is important for early diagnosis, clinical follow-up, and genetic counseling. HL due to mutations in COL11A2, encoding collagen type XI alpha-2, can be non-syndromic autosomal-dominant or autosomal-recessive, and also syndromic as in Otospondylomegaepiphyseal Dysplasia, Stickler syndrome type III, and Weissenbacher-Zweymuller syndrome. However, thus far only one mutation co-segregating with autosomal recessive non-syndromic hearing loss (ARNSHL) in a single family has been reported. In this study, whole exome sequencing of two consanguineous families with ARNSHL from Tunisia and Turkey revealed two novel causative COL11A2 mutations, c.109G > T (p.Ala37Ser) and c.2662C > A (p.Pro888Thr). The variants identified co-segregated with deafness in both families. All homozygous individuals in those families had early onset profound hearing loss across all frequencies without syndromic findings. The variants are predicted to be damaging the protein function. The p.Pro888Thr mutation affects a -Gly-X-Y- triplet repeat motif. The novel p.Ala37Ser is the first missense mutation located in the NC4 domain of the COL11A2 protein. Structural model suggests that this mutation will likely obliterate, or at least partially compromise, the ability of NC4 domain to interact with its cognate ligands. In conclusion, we confirm that COL11A2 mutations cause ARNSHL and broaden the mutation spectrum that may shed new light on genotype-phenotype correlation for the associated phenotypes and clinical follow-up.
authors: Laboratoire Procédés de Criblage Moléculaire et Cellulaire, Centre de Biotechnologie de Sfax, Université de Sfax, Route sidimansour Km 6, BP '1177', 3018, Sfax, Tunisia.
authors: Imen
authors: I
authors: Chakchouk
authors: M'hamed
authors: M
authors: Grati
authors: Guney
authors: G
authors: Bademci
authors: Mariem
authors: M
authors: Bensaid
authors: Qi
authors: Q
authors: Ma
authors: Amine
authors: A
authors: Chakroun
authors: Joseph
authors: J
authors: Foster
authors: Denise
authors: D
authors: Yan
authors: Duygu
authors: D
authors: Duman
authors: Oscar
authors: O
authors: Diaz-Horta
authors: Abdelmonem
authors: A
authors: Ghorbel
authors: Rahul
authors: R
authors: Mittal
authors: Amjad
authors: A
authors: Farooq
authors: Mustafa
authors: M
authors: Tekin
authors: Saber
authors: S
authors: Masmoudi
authors: Xue Zhong
authors: XZ
authors: Liu
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D024161:Collagen Type XI / Q000737:chemistry / Q000235:genetics*; D003241:Consanguinity; D059472:Exome / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA / Q000379:methods; D017386:Sequence Homology, Amino Acid
chemical_list: C499319:COL11A2 protein, human; D024161:Collagen Type XI
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