Abstract
Until now, over 30 loci have been identified by linkage analysis of affected families that segregate non-syndromic and dominantly inherited forms of hearing impairment (DFNA). A German family with a non-syndromic progressive hearing impairment transmitted in autosomal dominant mode was linked to 19q13.3-q13.4 by a genome-wide scan. Due to the low lod-score (1.85 at θ=0.05) for APOC2-locus we extended the fine mapping attempt with further markers in the same chromosomal region. This resulted in significant evidence for linkage to the markers D19S246 and D19S553 (two-point lod-score of 4.05 and 3.55 at θ=0.0) and a candidate critical region of 14 cM between markers D19S412 and D19S571. This region shows partial overlap with the previously reported DFNA4 critical region. The human gene BAX is orthologous to the rodent Bcl2-related apoptosis gene that is temporally expressed during the postnatal period in the developing inner ear of the mouse. BAX, mapping at a distance of no more than 0.73 cM distally to marker D19S553 appeared a likely candidate in our pedigree but genomic sequencing of coding regions and exon/intron boundaries excluded disease-related mutations. However, additional ESTs in the same region remain to be tested.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Kalatzis V, Petit C . The fundamental and medical impacts of recent progress in research on hereditary hearing loss Hum Mol Genet 1998 7: 1589–1597
Skvorak AB, Weng Z, Yee AJ, Robertson NG, Morton CC . Human cochlear expressed sequence tags provide insight into cochlear gene expression and identify candidate genes for deafness Hum Mol Genet 1999 3: 439–452
Adato A, Raskin L, Petit C, Bonne-Tamir B . Deafness heterogeneity in a Druze isolate from the Middle East: novel OTOF and PDS mutations, low prevalence of GJB2 35delG mutation and indication for a new DFNB locus Eur J Hum Genet 2000 8: 437–442
Prezant TR, Agapian JV, Bohlman MC et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness Nature Genet 1993 4: 289–294
Torroni A, Cruciani F, Rengo C et al. The A1555G mutation in the 12S rRNA gene of human mtDNA: recurrent origins and founder events in families affected by sensorineural deafness Am J Hum Genet 1999 65: 1349–1358
Petit C . Genes responsible for human hereditary deafness: symphony of a thousand Nature Genet 1996 14: 385–391
VanCamp G, Smith RJH . Hereditary hearing loss homepage 2000 http:dnalab-www.uia.ac.be/dnalab/hhh
Van Laer L, Huizing EH, Verstreken M et al. Nonsyndromic hearing impairment is associated with a mutation in DFNA5 Nature Genet 1998 2: 194–197
Chen AH, Ni L, Fukushima K et al. Linkage of a gene for dominant non-syndromic deafness to chromosome 19 Hum Mol Genet 1995 4: 1073–1076
Miller SA, Dykes DD, Polesky HF . A simple salting out procedure for extracting DNA from human nucleated cells Nucl Acids Res 1985 16: 1215
Lathrop GM, Lalouel JM, Julier C, Ott J . Strategies for multilocus linkage analysis in humans Proc Natl Acad Sci USA 1984 81: 3443–3446
Dib C, Faure S, Fizames C et al. A comprehensive genetic map of the human genome based on 5,264 microsatellites Nature 1996 380: 152–154
Yamamoto H, Sawai H, Perucho M . Frameshift somatic mutations in gastrointestinal cancer of the microsatellite mutator phenotype Cancer Res 1997 57: 4420–4426
Oeken J, König S . Formen monosymptomatischer hereditärer Schallempfindungsschwerhörigkeiten und Taubheiten im Umkeis von Leipzig HNO 1993 41: 301–310
Huygen PLM, Verhagen WIM, Noten JFP . Auditory abnormalities, including ‘precocious prebycusis’ in myotonic dystrophy Audiology 1994 33: 73–84
Verhagen WIM, Bruggen PL, Huygen PLM . Oculomotor, auditory, and vestibular responses in myotonic dystrophy Arch Neurol 1992 49: 954–960
Apte SS, Mattei MG, Olson B . Mapping of the human BAX gene to chromosome 19q13.3-q13.4 and isolation of a novel alternatively spliced transcript, BAXδ Genomics 1995 26: 592–594
Ishii N, Wanaka A, Ohno K et al. Localization of bcl-2, bax, and bcl-x mRNAs in the developing inner ear of the mouse Brain Res 1996 726: 123–128
Acknowledgements
The authors are grateful to the family members for participating. This study was supported by the program fortüne (No. 591.0), BMBF (Fö 01KS9602) and the Interdisciplinary Center of Clinical Research (IZKF) Tübingen.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mirghomizadeh, F., Bardtke, B., Devoto, M. et al. Second family with hearing impairment linked to 19q13 and refined DFNA4 localisation. Eur J Hum Genet 10, 95–99 (2002). https://doi.org/10.1038/sj.ejhg.5200769
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.ejhg.5200769
