Abstract
We ascertained two large Pakistani consanguineous families (PKDF231 and PKDF608) segregating profound hearing loss, vestibular dysfunction, and retinitis pigmentosa; the defining features of Usher syndrome type 1 (USH1). To date, seven USH1 loci have been reported. Here, we map a novel locus, USH1K, on chromosome 10p11.21–q21.1. In family PKDF231, we performed a genome-wide linkage screen and found a region of homozygosity shared among the affected individuals at chromosome 10p11.21–q21.1. Meiotic recombination events in family PKDF231 define a critical interval of 11.74 cM (20.20 Mb) bounded by markers D10S1780 (63.83 cM) and D10S546 (75.57 cM). Affected individuals of family PKDF608 were also homozygous for chromosome 10p11.21–q21.1-linked STR markers. Of the 85 genes within the linkage interval, PCDH15, GJD4, FZD4, RET and LRRC18 were sequenced in both families, but no potential pathogenic mutation was identified. The USH1K locus overlaps the non-syndromic deafness locus DFNB33 raising the possibility that the two disorders may be caused by allelic mutations.
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Acknowledgements
We are grateful to the families who made this research possible. These families were ascertained using the intramural funds from NIDCD DC000039-15 to Thomas B Friedman. We thank Khitab Gul, R Amjad Ali and Hashim Raza for technical assistance and Tom Friedman for his suggestions regarding this manuscript. ZMA is a recipient of an RPB Career Development Award. This work was supported by the Higher Education Commission and Ministry of Science and Technology, Islamabad, Pakistan, to Shaikh Riazuddin the International Center for Genetic Engineering and Biotechnology, Trieste, Italy under project CRP/PAK08-01 contract no. 08/009 to Shaikh Riazuddin Cincinnati Children’s Hospital Research Foundation (CCHMC) Intramural Research Funds, to SR and ZMA; Action on Hearing Loss grant to SR; National Institute on Deafness and Other Communication Disorders (NIDCD/NIH) research grants R00 DC009287 to ZMA and R01 DC011803 to SR.
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Jaworek, T., Bhatti, R., Latief, N. et al. USH1K, a novel locus for type I Usher syndrome, maps to chromosome 10p11.21–q21.1. J Hum Genet 57, 633–637 (2012). https://doi.org/10.1038/jhg.2012.79
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DOI: https://doi.org/10.1038/jhg.2012.79
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