A new locus for nonsyndromic deafness DFNB49 maps to chromosome 5q12.3-q14.1
- 214 Downloads
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.
KeywordsRetinitis Pigmentosa Usher Syndrome Nonsyndromic Hearing Loss Nonsyndromic Deafness Deafness Gene
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).
- Ahmed ZM, Riazuddin S, Ahmad J, Bernstein SL, Guo Y, Sabar MF, Sieving P, Riazuddin S, Griffith AJ, Friedman TB, Belyantseva IA, Wilcox ER (2003a) PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23. Hum Mol Genet 12:3215–3223CrossRefPubMedGoogle Scholar
- Ben-Yosef T, Belyantseva IA, Saunders TL, Hughes ED, Kawamoto K, Van Itallie CM, Beyer LA, Halsey K, Gardner DJ, Wilcox ER, Rasmussen J, Anderson JM, Dolan DF, Forge A, Raphael Y, Camper SA, Friedman TB (2003) Claudin 14 knockout mice, a model for autosomal recessive deafness DFNB29, are deaf due to cochlear hair cell degeneration. Hum Mol Genet 12:2049–2061CrossRefPubMedGoogle Scholar
- Bork JM, Peters LM, Riazuddin S, Bernstein SL, Ahmed ZM, Ness SL, Polomeno R, Ramesh A, Schloss M, Srisailpathy CR, Wayne S, Bellman S, Desmukh D, Ahmed Z, Khan SN, Kaloustian VM, Li XC, Lalwani A, Riazuddin S, Bitner-Glindzicz M, Nance WE, Liu XZ, Wistow G, Smith RJ, Griffith AJ, Wilcox ER, Friedman TB, Morell RJ (2001) Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. Am J Hum Genet 68:26–37CrossRefPubMedGoogle Scholar
- Cohen MM, Gorlin RJ (1995) Epidemiology, etiology and genetic patterns. In: Gorlin RJ, Toriello HV, Cohen MM (eds) Hereditary hearing loss and its syndromes. Oxford University Press, Oxford, pp 43–61Google Scholar
- Park HJ, Shaukat S, Liu XZ, Hahn SH, Naz S, Ghosh M, Kim HN, Moon SK, Abe S, Tukamoto K, Riazuddin S, Kabra M, Erdenetungalag R, Radnaabazar J, Khan S, Pandya A, Usami SI, Nance WE, Wilcox ER, Riazuddin S, Griffith AJ (2003) Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness. J Med Genet 40:242–248CrossRefPubMedGoogle Scholar
- Vahava O, Morell R, Lynch ED, Weiss S, Kagan ME, Ahituv N, Morrow JE, Lee MK, Skvorak AB, Morton CC, Blumenfeld A, Frydman M, Friedman TB, King MC, Avraham KB (1998) Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans. Science 279:1950–1954CrossRefPubMedGoogle Scholar
- Wilcox ER, Burton QL, Naz S, Riazuddin S, Smith TN, Ploplis B, Belyantseva I, Ben-Yosef T, Liburd NA, Morell RJ, Kachar B, Wu DK, Griffith AJ, Riazuddin S, Friedman TB (2001) Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29. Cell 104:165–172CrossRefPubMedGoogle Scholar