Compound heterozygous MYO7A mutations segregating Usher syndrome type 2 in a Han family.
OBJECTIVE
Identification of rare deafness genes for inherited congenital sensorineural hearing impairment remains difficult, because a large variety of genes are implicated. In this study we applied targeted capture and next-generation sequencing to uncover the underlying gene in a three-generation Han family segregating recessive inherited hearing loss and retinitis pigmentosa.


METHODS
After excluding mutations in common deafness genes GJB2, SLC26A4 and the mitochondrial gene, genomic DNA of the proband of a Han family was subjected to targeted next-generation sequencing. The candidate mutations were confirmed by Sanger sequencing and subsequently analyzed with in silico tools.


RESULTS
An unreported splice site mutation c.3924+1G > C compound with c.6028G > A in the MYO7A gene were detected to cosegregate with the phenotype in this pedigree. Both mutations, located in the evolutionarily conserved FERM domain in myosin VIIA, were predicted to be pathogenic. In this family, profound sensorineural hearing impairment and retinitis pigmentosa without vestibular disorder, constituted the typical Usher syndrome type 2.


CONCLUSION
Identification of novel mutation in compound heterozygosity in MYO7A gene revealed the genetic origin of Usher syndrome type 2 in this Han family.
['Zong|Ling|L|', 'Chen|Kaitian|K|', 'Wu|Xuan|X|', 'Liu|Min|M|', 'Jiang|Hongyan|H|']
D000293:Adolescent D000328:Adult D044466:Asians D002648:Child D004252:DNA Mutational Analysis D005190:Family D005260:Female D006579:Heterozygote D059014:High-Throughput Nucleotide Sequencing D006801:Humans D008297:Male D008875:Middle Aged D009154:Mutation D000081412:Myosin VIIa D009218:Myosins D010375:Pedigree D010641:Phenotype D052245:Usher Syndromes D055815:Young Adult
MYO7A Usher syndrome Hearing Targeted next-generation sequencing Nonsense-mediated mRNA decay