DFNB68, a novel autosomal recessive non-syndromic hearing impairment locus at chromosomal region 19p13.2
- 127 Downloads
From a large collection of families with autosomal recessive non-syndromic hearing impairment (NSHI) from Pakistan, linkage has been established for two unrelated consanguineous families to 19p13.2. This new locus was assigned the name DFNB68. A 10 cM genome scan and additional fine mapping were carried out using microsatellite marker loci. Linkage was established for both families to DFNB68 with maximum multipoint LOD scores of 4.8 and 4.6. The overlap of the homozygous regions between the two families was bounded by D19S586 and D19S584, which limits the locus interval to 1.9 cM and contains 1.4 Mb. The genes CTL2, KEAP1 and CDKN2D were screened but were negative for functional sequence variants.
KeywordsHair Cell Hearing Impairment Multipoint Linkage Analysis Autosomal Recessive Mode DFNB68 Locus
We thank the two families who participated in this research. We are also grateful to Xuan Zhang for assistance with the figures. This work was supported by the Higher Education Commission, Pakistan, and National Institutes of Health, National Institute of Deafness and other Communication Disorders grant R01-DC03594. Genotyping services were provided by the CIDR and the NHLBI Mammalian Genotyping Service (Marshfield, WI, USA). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, Contract Number N01-HG-65403.
- Chen A, Wayne S, Bell A, Ramesh A, Srisailapathy CRS, Scott DA, Sheffield VC, Van Hauwe P, Zbar RIS, Ashley J, Lovett M, Van Camp G, Smith RJH (1997) New gene for autosomal recessive non-syndromic hearing loss maps to either chromosome 3q or 19p. Am J Med Genet 71:467–471PubMedCrossRefGoogle Scholar
- Grimberg J, Nawoschik S, Bellusico L, McKee R, Turck A, Eisenberg A (1999) A simple and efficient non-organic procedure for the isolation of genomic DNA from Blood. Nucleic Acid Res 17:83–90Google Scholar
- Holme RH, Bussoli TJ, Steel KP (2002) Table of gene expression in the developing ear. URL: http://www.ihr.mrc.ac.uk/Hereditary/genetable/index.shtml
- International Human Genome Sequence Consortium (2001) Initial sequence and analysis of the human genome. Nature 409:860–921Google Scholar
- Nair TS, Kozma KE, Hoefling NL, Kommareddi PK, Ueda Y, Gong TW, Lomax MI, Lansford CD, Telian SA, Satar B, Arts HA, El-Kashlan HK, Berryhill WE, Raphael Y, Carey TE (2004) Identification and characterization of choline transporter-like protein 2, an inner ear glycoprotein of 68 and 72 kDa that is the target of antibody-induced hearing loss. J Neurosci 24:1772–1779PubMedCrossRefGoogle Scholar
- Rozen S, Skaletsky HJ (2000) Primer3 on the WWW for general users and for biologist programmers. In: Krawetz S, Misener S (eds) Bioinformatics methods and protocols: methods in molecular biology. Humana Press, NJ, pp 365–386Google Scholar
- The Hearing Research Group at Brigham and Women’s Hospital (2002) Human Cochlear cDNA library and EST database. http://www.hearing.bwh.harvard.edu/estinfo.HTM
- Van Camp G, Smith RJH (2005) Hereditary hearing loss. Homepage: http://www.webhost.ua.ac.be/hhh/