Abstract
Cosegregation of markers on chromosome 5q12.3-q14.1 with profound congenital deafness in two Pakistani families (PKDF041 and PKDF141) defines a new recessive deafness locus, DFNB49. A maximum two-point lod score of 4.44 and 5.94 at recombination fraction θ=0 was obtained for markers D5S2055 and D5S424 in families PKDF041 and PKDF141, respectively. Haplotype analysis revealed an 11 cM linkage region flanked by markers D5S647 (74.07 cM) and D5S1501 (85.25 cM). Candidate deafness genes in this region include SLC30A5, OCLN, GTF2H2, and BTF3, encoding solute carrier family 30 (zinc transporter) member 5, occludin, RNA polymerase II transcription initiation factor, and basic transcription factor 3, respectively. Sequence analysis of the coding exons of SLC30A5 in DNA samples from two affected individuals of families PKDF041 and PKDF141 revealed no mutation. The mapping of DFNB49 further confirms the heterogeneity underlying autosomal recessive forms of nonsyndromic deafness.
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Acknowledgements
We are grateful to the families for their participation in this study. We thank Dr. Dennis Drayna and Dr. Robert Morell for their comments on this manuscript, and Sabiha Nazli and Muhammad Awais for their technical assistance. This study was supported by the Higher Education Commission, Islamabad, Pakistan; the Ministry of Science and Technology, Islamabad, Pakistan; and the International Center for Genetic Engineering and Biotechnology, Trieste, Italy under project CRP/PAK02-01 (contract no. 02/013). Part of this study in USA was supported by intramural funds from the National Institute on Deafness and Other Communication Disorders (1ZO1 DC000035-07 and 1ZO1 DC000039-07).
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Ramzan, K., Shaikh, R.S., Ahmad, J. et al. A new locus for nonsyndromic deafness DFNB49 maps to chromosome 5q12.3-q14.1. Hum Genet 116, 17–22 (2005). https://doi.org/10.1007/s00439-004-1205-8
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DOI: https://doi.org/10.1007/s00439-004-1205-8