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Pendred syndrome (goitre and sensorineural hearing loss) maps to chromosome 7 in the region containing the nonsyndromic deafness gene DFNB4

Nature Genetics volume 12, pages 421–423 (1996)Cite this article

Abstract

Inherited causes account for about 50% of Individuals presenting with childhood (prelingual) hearing loss, of which 70% are due to mutation in numerous single genes which impair auditory function alone (non-syndromic)1. The remainder are associated with other developmental anomalies termed syndromic deafness. Genes responsible for syndromic forms of hearing loss include the COL4A5 gene in Alport syndrome and the PAX3 and MITF genes in Waardenburg syndrome2. Pendred syndrome is an autosomal recessive disorder associated with developmental abnormalities of the cochlea, sensorineural hearing loss and diffuse thyroid enlargement (goitre)3,4. Pendred syndrome is the most common syndromal form of deafness, yet the primary defect remains unknown. We have established a panel of 12 families with two or more affected individuals and used them to search for the location of the Pendred gene by linkage analysis. We excluded localization to four previously mapped nonsyndromic deafness loci but obtained conclusive evidence for linkage of the Pendred syndrome gene to microsatellite markers on chromosome 7q31 (D7S496 Zmax 7.32, Qmax = 0). This region contains a gene, DFNBL, for autosomal recessive non-syndromic sensorineural hearing loss. Multipoint analysis indicates that DFNB4 and Pendred syndrome co-localize to the same 5.5 centiMorgan (cM) interval flanked by D7S501 and D7S523. These data raise the possibility that Pendred syndrome is either allelic with DFNB4 or may represent an inherited contiguous gene disorder, not clinically manifest in the heterozygote.

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Author notes

  1. Beth Coyle and Rebecca Coffey: B.C. and R.C. contributed equally to this work

Authors and Affiliations

  1. Department of Genetics and Department of Medicine and Therapeutics, University of Leicester, Adrian Building, University Road, Leicester, LE1 7RH, UK

    Beth Coyle, John A.L. Armour, Eleanor Gausden & Richard Trembath

  2. Department of Clinical Genetics and Fetal Medicine, Institute of Child Health, University of London, 30 Guilford Street, London, WC1N 1EH, UK

    Rebecca Coffey, Marcus Pembrey & William Reardon

  3. Division of Endocrinology, Department of Paediatrics, Rambam Medical Centre, POB 9649, Haifa, 31096, Israel

    Ze'ev Hochberg

  4. Departments of Endocrinology and Nuclear Medicine, St. Bartholomews Hospital, West Smithfield, London, EC1 A 7BE, UK

    Ashley Grossman & Keith Britton

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Coyle, B., Coffey, R., Armour, J. et al. Pendred syndrome (goitre and sensorineural hearing loss) maps to chromosome 7 in the region containing the nonsyndromic deafness gene DFNB4. Nat Genet 12, 421–423 (1996). https://doi.org/10.1038/ng0496-421

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