Novel mutation located in EC7 domain of protocadherin-15 uncovered by targeted massively parallel sequencing in a family segregating non-syndromic deafness DFNB23.
OBJECTIVE
Hereditary hearing loss is a clinically and genetically heterogeneous disorder associated with mutations of a large number of diverse genes. In this study we applied targeted capture and massively parallel sequencing to identify the disease-causing gene of a Chinese family segregating recessive inherited deafness.


METHODS
After excluding mutations in common deafness genes GJB2, SLC26A4, mitochondrial m.1555A>G, genomic DNA of the proband of family GDSW24 was subjected to targeted next-generation sequencing. Subsequently, a candidate homozygous mutation was confirmed by Sanger sequencing.


RESULTS
A novel PCDH15 c.2367_2369delTGT/p.V788-homozygous mutation was detected. In this family, no obvious vestibular disorder was found. The in-frame mutation c.2367_2369delTGT is located in the evolutionarily conserved EC7 domain of Protocadherin-15 and was predicted to be pathogenic.


CONCLUSIONS
The novel homozygous mutation in a family segregating non-syndromic hearing loss family supports previous reported observations that PCDH15 does not only causes Usher syndrome type 1F, but also DFNB23.
Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou 510080, PR China.
Yuan
Y
Zhan
Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou 510080, PR China.
Min
M
Liu
Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou 510080, PR China.
DeHua
D
Chen
Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou 510080, PR China.
KaiTian
K
Chen
Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address: jhongy@mail.sysu.edu.cn.
HongYan
H
Jiang
D000293:Adolescent; D000328:Adult; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D000072259:Connexin 26; D017630:Connexins; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055815:Young Adult
C498835:CDHR15, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D017630:Connexins; C000607042:GJB2 protein, human; D005819:Genetic Markers; D000072259:Connexin 26
DFNB23; PCDH15; Protocadherin-15; Targeted next-generation sequencing