New Modes of GPCR Signalling

Identification a Novel MYO6 Mutation Associated with Autosomal
Dominant Non-Syndromic Hearing Impairment in a Large Chinese
Family
Yulei Li1,2, Zhenping Xu1,2, Xiangyang Zhang1, Juan Li1, Jing Yu Liu1*
1Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life
Science and Technology, Center for Human Genome Research, Huazhong University
of Science and Technology, 430074, Wuan, Hubei, P. R. China; 2Department of Life
Science and Technique, Xinxiang Medical University, Xinxiang, 453003, China)
Objectives: Hearing impairment is a disorder of partial or complete hearing loss, it is
caused by organic or functional pathological changes in the human auditory system. Hearing
impairment have an estimated incidence rate of approximately 1 in 500 newborns with bilateral
congenital sensorineural hearing loss≥40dB in developed countries. And the ratio up to 2.7‰
for the age of 5. In the adolescent, this number rises to 3.5‰. Genetic factor is the most
important nosogenesis among all the factors. Most of the inherited cases are non-syndromic,
with the only symptom of auditory dysfunction, not accompanied with other malformation or
disorder. Most of the non-syndromic hearing impairment (NSHI) is caused by monogenic
mutation, and they are genetically heterogeneity. Many autosomal dominant NSHI genes have
been identified. Most of these genes have a high expression or specially expressed in the inner
ear cells. By the molecular basis of these studies, it gives us a further understands of the
physiological mechanism of auditory system and the pathological basis of hearing
impairment.Methods: Linkage analysis was carried out by STR Markers flanking all known
autosomal dominant NSHI genes and direct DNA sequence for the proband was used to
mutation analysis by ABI PRISM 3100 Genetic Analyzer.Results: A large Chinese Han family
with an autosomal dominant non-syndromic hearing impairment have been identified and
characterized. Linkage analysis of genotyping data from the family showed the DFNA22 locus
can not be excluded. There is only one candidate gene MYO6 in this locus which is responsible
for NSHI. Mutational analysis showed a novel missense mutation c.599A>G in exon 8 was
found in proband, it was co-segregated with the affected individuals in the family and did not
exist in the unaffected family members and 100 unrelated normal controls. The mutation results
in a substitution of an asparagine residue by a serine residue at codon 200 (p.N200S). The
p.N200S occurred in the motor domain near the ATP binding site of myosin VI, and the N200
residue is evolutionally highly conserved from flagellum to human.Conclusion: It is presumed
that the mutation p.N200S in the motor domain maybe affect the generation of mechanical force
in myosin VI, and lead to the dysfunction of inner ear hair cell, and eventually result in the
hearing impairment.
Key Words: non-syndromic hearing impairment, mutation analysis, myosin VI, p.N200S,
motor domain
*Correspondence to: Dr. J. Y. Liu, liujy@mail.hust.edu.cn