Abstract
There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132 and PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild-to-profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling and molecular epidemiology of hearing loss among Pakistanis.
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Acknowledgements
We are grateful to the families who made this research possible. This work was supported by Cincinnati Children's Hospital Research Foundation (CCHMC) intramural research funds to Sheikh Riazuddin and ZMA, the National Institute on Deafness and Other Communication Disorders (NIDCD/NIH) research Grant R00-DC009287-03, a Career Development Award from RPB to ZMA. Work in Pakistan was supported by the Higher Education Commission to Sheikh Riazuddin, Islamabad; EMRO/WHO-COMSTECH and Ministry of Science and Technology (MoST) to Sheikh Riazuddin, Islamabad; the International Center for Genetic Engineering and Biotechnology, Trieste, Italy under project CRP/PAK08-01 Contract no. 08/009 to Sheikh Riazuddin. Part of this study carried out in the USA was supported by intramural funds from the NIDCD/NIH (Z01-DC00039-14) to TBF.
Note : While this manuscript was in press, two independent studies published in the May 2011 issue of American Journal of Human Genetics,41, 42 reported mutations of SMPX as another cause of X-linked nonsyndromic hearing loss in humans.
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Waryah, A., Ahmed, Z., Binder, M. et al. Molecular and clinical studies of X-linked deafness among Pakistani families. J Hum Genet 56, 534–540 (2011). https://doi.org/10.1038/jhg.2011.55
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DOI: https://doi.org/10.1038/jhg.2011.55
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