Screening of Myo7A Mutations in Iranian Patients with Autosomal Recessive Hearing Loss from West of Iran
Abstract
Background: Hearing loss (HL) is the most frequent neurosensory impairment. HL is highly heterogeneous defect. This disorder affects 1 out of 500 newborns. This study aimed to determine the role of DFNB2 locus and frequency of MYO7A gene mutations in a population from west of Iran.
Methods: Thirty families investigated in Shahrekord University of Medical Sciences in 2014, genetic linkage analysis via four short tandem repeat markers linked to MYO7A was performed for two consanguineous families originating from Hamedan (family-13) and Chaharmahal-Bakhtiari (family-32) provinces of Iran, co-segregating autosomal recessive HL and showed no mutation in GJB2 gene in our preliminary investigation. All 49 coding exons and exon- intron boundaries of the MYO7A gene were amplified by PCR and analyzed using direct DNA sequencing.
Results: Two of families displayed linkage to DFNB2. Family-13 segregated a homozygous missense mutation (c.6487G>A) in exon 48 that results in a p.G2163S amino acid substitution in C-terminal domain of the myosin VIIA protein. While family-32 segregated a homozygous nonsense mutation (c.448 C>T) in exon five, resulting in a premature truncation at amino acid position 150 (p.Arg150X) in the motor domain of this protein.
Conclusion: Mutation frequency of MYO7A gene in different populations of Iran as well as cause of HL in most cases are still unknown and more extensive studies have to be done.
Asgharzade S, Chaleshtori MH, Tabatabaiefar MA, Reiisi S, Modarressi MH. Mutation in the second exon of MYO15A in nonsyndromic hearing loss in Iranian Arabs (2016). Genetika, 48 (2): 587 -596.
Camp GV, Smith R (2014). The Hereditary Hearing loss Homepage: http://hereditaryhearingloss.org.
Odronitz F, Kollmar M. Drawing the tree of eukaryotic life based on the analysis of 2,269 manually annotated myosins from 328 species (2007). Genome Biol, 8 (9): R196.
Brownstein Z, Abu-Rayyan A, Karfunkel-Doron D, Sirigu S, Davidov B, et al. (2014). Novel myosin mutations for hereditary hearing loss revealed by targeted genomic capture and massively parallel sequencing. Eur J Hum Genet, 22(6):768-75.
Hartman MA, Spudich JA (2012). The myosin superfamily at a glance. J Cell Sci, 125 (Pt7): 1627-32.
Sang Q, Yan X, Wang H, Feng R, Fei X, Ma D, et al (2013). Identification and functional study of a new missense mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11). PloS One, 8 (1): e55178.
Ma Y, Xiao Y, Zhang F, Han Y, Li J, Xu L, et al (2016). Novel compound heterozygous mutations in MYO7A gene associated with autosomal recessive sensorineural hearing loss in a Chinese family. Int J Pediatr Otorhinolaryngol, 83:179-85.
Hildebrand MS, Thorne NP, Bromhead CJ, Kahrizi K, Webster JA, Fattahi Z, et al (2010). Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation. Clin Genet, 77 (6): 563-71.
Sloan-Heggen CM, Babanejad M, Beheshtian M, Simpson AC, Booth KT, Ardalani F, et al (2015). Characterizing the spectrum of autosomal recessive hereditary hearing loss in Iran. J Med Genet, 52(12):823-9.
Johns MB, Paulus-Thomas JE (1989). Purification of human genomic DNA from whole blood using sodium perchlorate in place of phenol. Anal Biochem, 180 (2):276-8.
Lindner TH, Hoffmann K (2005). Easy LINKAGE: a PERL script for easy and automated two-/multi-point linkage analyses. Bioinformatics, 21 (3): 405-7.
Thiele H, Nürnberg P (2005). HaploPainter: a tool for drawing pedigrees with complex haplotypes. Bioinformatics, 21 (8): 1730-2.
Tabatabaiefar M, Alasti F, Zohour MM, Shariati L, Farrokhi E, Farhud D, et al (2011). Genetic linkage analysis of 15 DFNB loci in a group of Iranian families with autosomal recessive hearing loss. Iran J Public Health, 40 (2): 34-38.
Chaleshtori MH, Farhud D, Crosby A, Farrokhi E, Jafari HP, Samani KG, et al (2008). Molecular pathology of 6 novel GJB2 allelic variants detected in familial and sporadic Iranian non-syndromic hearing loss cases. Iran J Public Health, 37(3):9-18.
Chaleshtori MH, Farhud D, Patton M (2007). Congratulation to margaret chan familial and sporadic GJB2-Related Deafness in Iran: Review of Gene Mutations. Iran J Public Health. 36 (1):1-14.
Mahdieh N, Rabbani B, Shirkavand A, Bagherian H, Movahed ZS, Fouladi P, et al. (2011) Impact of consanguineous marriages in GJB2-related hearing loss in the Iranian population: A report of a novel variant. Genet Test Mol Biomarkers, 15 (7-8): 489-93.
Asgharzade S, Tabatabaiefar MA, Modarressi MH, Ghahremani MH, Reiisi S, Tahmasebi P. et al. (2017). A novel TECTA mutation causes ARNSHL. Int J Pediatr Otorhinolaryngol. 92: 88-93.
Guilford P, Ayadi H, Blanchard S, Chaib H, Le Paslier D, Weissenbach J, et al (1994). A human gene responsible for neurosensory, non-syndromic recessive deafness is a candidate homologue of the mouse sh-1 gene. Hum Mol Gen, 3 (6): 989-93.
Liu X-Z, Walsh J, Mburu P, Kendrick-Jones J, Cope MJT, Steel KP, et al. (1997). Mutations in the myosin VIIA gene cause non-syndromic recessive deafness. Nat Genet, 16 (2): 188-90.
Weil D, Levy G, Sahly I, Levi-Acobas F, Blanchard S, El-Amraoui A, et al. (1996). Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in developing sensory epithelia. Proc Natl Acad Sci U S A, 93 (8): 3232-7.
Riazuddin S, Nazli S, Ahmed ZM, Yang Y, Zulfiqar F, Shaikh RS, et al. (2008). Mutation spectrum of MYO7A and evaluation of a novel nonsyndromic deafness DFNB2 allele with residual function. Hum Mutat, 29 (4): 502-11.
Su M-C, Yang J-J, Su C-C, Hsin C-H, Li S-Y (2009). Identification of novel variants in the Myosin VIIA gene of patients with nonsyndromic hearing loss from Taiwan. Int J Pediatr Otorhinolaryngol, 73 (6): 811-5.
Babanejad M, Fattahi Z, Bazazzadegan N, Nishimura C, Meyer N, Nikzat N, et al. (2012). A comprehensive study to determine heterogeneity of autosomal recessive nonsyndromic hearing loss in Iran. Am J Med Genet, 158A (10): 2485-92.
Rizel L, Safieh C, Shalev SA, Mezer E, Jabaly-Habib H, Ben-Neriah Z, et al. (2011). Novel mutations of MYO7A and USH1G in Israeli Arab families with Usher syndrome type 1. Mol Vis, 17: 3548-3555.
Hasson T, Heintzelman MB, Santos-Sacchi J, Corey DP, Mooseker MS (1995). Expression in cochlea and retina of myosin VIIa, the gene product defective in Usher syndrome type 1B. Proc Natl Acad Sci U S A, 92 (21): 9815-9.
Shahin H, Walsh T, Rayyan AA, Lee MK, Higgins J, Dickel D, et al. (2010). Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families. Eur J Hum Genet, 18 (4): 407-13.
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| Issue | Vol 46 No 1 (2017) | |
| Section | Original Article(s) | |
| Keywords | ||
| MYO7A Deafness Linkage analysis DFNB2 Iran | ||
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