Phenotype and genotype analysis of a Chinese family with prelingual X-linked hereditary hearing impairment.
BACKGROUND
X-linked hearing impairment is clinically and genetically a heterogeneous disease. Although many disorders manifest with hearing loss, a limited number of sex-linked loci and only one gene (POU3F4) have been shown to be implicated in X-linked non-syndromic hearing impairment. In the present study, we have performed a clinical and genetic analysis of a Chinese family with X-linked non-syndromic hearing loss, with emphasis on audiological findings and genomic mapping.


METHODS
The clinical features of Family JX01 were evaluated by physical and audiometric examination in eighteen family members. Mutation screening of POU3F4 was identified by polymerase chain reaction (PCR) amplification and sequencing. Molecular evaluation consisted of X-chromosome wide genotyping by microsatellite makers (STR), followed by analyzing using MLINK computer program.


RESULTS
Five affected males demonstrated bilateral, symmetrical sensorineural and profound hearing loss. The hearing impairment started prelingual. The female carriers did not have any complain of hearing loss, however, two of them were tested with milder loss with high frequency. No causative mutations in POU3F4 gene were detected by DNA sequencing. Linkage analysis indicated that the responsible gene was linked to locus DXS1227 (maximum lod score = 2.04 at theta = 0).


CONCLUSIONS
The affected males in Family JX01 have profound prelingual sensorineural hearing impairment. In addition, two female carriers showed mild to moderate hearing losses. However, none of females complained of any hearing loss. Analysis of hereditary deafness in this family mapped most compatibly to the Xq27.2.
Han
Bing
B
Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Cheng
Jing
J
Yang
Shu-Zhi
SZ
Cao
Ju-Yang
JY
Shen
Wei-Dong
WD
Ji
Fei
F
Kang
Dong-Yang
DY
Zhang
Xin
X
Dai
Pu
P
Yuan
Hui-Jun
HJ
D044466:Asian People / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype