GENETICS OF HEARING LOSS

ABSTRACT

Approximately 1 in 1000 children is affected sporadically with congenital or early childhood-onset sensorineural hearing impairment/deafness. Approximately 50% have a genetic cause, with 70% nonsyndromal and 75% attributable to a mutation in an autosomal recessive gene. Studies of the recurrence of hearing impairment in the offspring of couples, both of whom have hearing impairment/deafness, have indicated that up to 100 genes are responsible for nonsyndromal sensorineural hearing impairment/deafness (NSSNHI/D). During the past 8 years, 28 autosomal recessive, 30 autosomal dominant, and 5 X-linked loci have been mapped; during the past 3 years, 6 autosomal recessive, 10 autosomal dominant, and 2 X-linked genes for NSSNHI/D have been cloned. It is now possible to offer mutation testing of children sporadically affected with NSSNHI/D to determine whether their hearing impairment is attributable to a genetic cause allowing precise Mendelian recurrence risk advice to be provided for couples in whom a mutation is identified.

KEYWORD

Hearing impairment - inheritance - molecular genetics

REFERENCES

• 1 Parving A. Epidemiology of hearing loss and aetiological diagnosis of hearing impairment in childhood.  Int J Pediatr Otorhinolaryngol . 1983;  5 151-165
• 2 Newton V. Aetiology of bilateral sensorineural hearing loss in young children.  J Laryngol Otol . 1985;  10(suppl) 1-57
• 3 Cohen M, Gorlin R. Epidemiology, etiology, and genetic patterns. In: Gorlin R, Toriello H, Cohen M, eds. Hereditary Hearing Loss and Its Syndromes Oxford: Oxford University Press 1995: 9-21
• 4 Fraser G R. Profound childhood deafness.  J Med Genet . 1964;  1 118-151
• 5 Fraser G. The Causes of Profound Deafness in Childhood.  Baltimore, MD: Johns Hopkins University Press; 1976
• 6 Parving A. Aetiologic diagnosis in hearing-impaired children-clinical value and application of a modern programme.  Int J Pediatr Otorhinolaryngol . 1984;  7 29-38
• 7 Chung C S, Brown K S. Family studies of early childhood deafness ascertained through the Clarke school for the deaf.  Am J Hum Genet . 1970;  22 630-644
• 8 Taylor I G, Hine W D, Brasier K. A study of the causes of hearing loss in a population of deaf children with special reference to genetic factors.  J Laryngol Otol . 1975;  89 899-914
• 9 Ben Arab S, Bonäiti-Pellié A, Belkahia A. An epidemiological and genetic study of congenital profound deafness in Tunisia (governorate of Nabuel).  J Med Genet . 1990;  27 29-33
• 10 van Rijn M P, Cremers C R J W. Causes of childhood deafness at a Dutch school for the hearing impaired. Ann Otol Rhinol Laryngol .  1991;  100 903-908
• 11 Chaurasia M K, Geddes N K. An analysis of the aetiology of early childhood deafness.  Clin Otolaryngol . 1991;  16 280-284
• 12 Marazita M L, Ploughman L M, Rawlings B. Genetic epidemiological studies of early-onset deafness in the U.S. school-age population.  Am J Hum Genet . 1993;  46 486-491
• 13 Wildervanck L. Audiometric examination of parents of children deaf from birth.  Arch Otolaryngol . 1957;  65 280-295
• 14 Liu X, Xu L. Nonsyndromic hearing loss: an analysis of audiograms.  Ann Otol Rhinol Laryngol . 1994;  103 428-433
• 15 Bieber F, Nance W. Hereditary hearing loss. In: Jackson C, Schimke N, eds. Clinical Genetics: A Course Book for Physicians New York: John Wiley & Sons 1979: 443-461
• 16 Majumder P P, Ramesh A, Chinnapan D. On the genetics of prelingual deafness.  Am J Hum Genet . 1989;  44 86-99
• 17 Newton V E. Genetic counselling for isolated hearing loss.  J Laryngol Otol . 1989;  103 12-15
• 18 Smith S. Recurrence risks. In: Ruben RJ, van der Water TR, Steel KP, eds. Genetics of Hearing Impairment Ann NY Acad Sci 1991 630: 203-211
• 19 Stevenson A, Cheeseman E. Hereditary deaf mutism, with particular reference to Northern Ireland.  Ann Hum Genet . 1956;  20 177-231
• 20 Nance W E, McConnell F E. Status and prospects of research in hereditary deafness.  Adv Hum Genet . 1973;  4 173-250
• 21 Costeff H, Dar H. Consanguinity analysis of congenital deafness in Northern Israel.  Am J Hum Genet . 1980;  32 64-68
• 22 Brownstein Z, Friedlander Y, Peritz E, Cohen T. Estimated number of loci for autosomal recessive severe nerve deafness within the Israeli Jewish population, with implications for genetic counseling.  Am J Med Genet . 1991;  41 306-312
• 23 León P E, Bonilla J A, Sanchez J R. Low frequency hereditary deafness in man with childhood onset.  Am J Hum Genet . 1981;  33 209-214
• 24 León P, Raventos H, Lynch E. The gene for an inherited form of deafness maps to chromosome 5q31.  Proc Natl Acad Sci USA . 1992;  89 5181-5184
• 25 Lander E, Botstein D. Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children.  Science . 1987;  236 1567-1570
• 26 Mueller R, Bishop D. Complex consanguinity and homozygosity mapping.  J Med Genet . 1993;  30 798-799
• 27 Kruglyak L, Daly M, Lander E. Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping.  Am J Hum Genet . 1995;  56 519-527
• 28 Guilford P, Ben Arab S, Blanchard S. A non-syndromic form of neurosensory, recessive deafness maps to the pericentromeric region of chromosome 13q.  Nature Genet . 1994;  6 24-28
• 29 Prezant T R, Agapian J V, Bohlman M C. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness.  Nature Genet . 1993;  4 289-294
• 30 Maw M A, Allen-Powell D R, Goodey R J. The contribution of the DFNB1 locus to neurosensory deafness in a Caucasian population.  Am J Hum Genet . 1995;  57 629-635
• 31 Gasparini P, Estivill X, Volpini V. Linkage of DFNB1 to non-syndromic neurosensory autosomal-recessive deafness in Mediterranean families.  Eur J Hum Genet . 1997;  5 83-88
• 32 Chaïb H, Lina-Granade G, Guilford P. A gene responsible for a dominant form of neurosensory nonsyndromic deafness maps to the NSRD1 recessive deafness gene interval.  Hum Mol Genet . 1994;  3 2219-2222
• 33 Kelsell D, Dunlop J, Stevens H. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness.  Nature . 1997;  387 80-83
• 34 Zelante L, Gasparini P, Estivill X. Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans.  Hum Mol Genet . 1997;  6 1605-1609
• 35 Denoyelle F, Weil D, Maw M A. Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene.  Hum Mol Genet . 1997;  12 2173-2177
• 36 Estivill X, Fortina P, Surrey S. Connexin-26 mutations in sporadic and inherited sensorineural deafness.  Lancet . 1999;  381 394-398
• 37 Lench N, Houseman M, Newton V. Connexin-26 mutations in sporadic non-syndromal sensorineural deafness.  Lancet . 1998;  351 415
• 38 Kelley P M, Harris D J, Comer B C. Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss.  Am J Hum Genet . 1998;  62 792-799
• 39 Morrell R J, Kim H J, Hood L. Mutations in the connexin 26 (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness.  N Engl J Med . 1998;  339 1500-1505
• 40 Scott D A, Kraft M L, Carmi R. Identification of mutations in the connexin 26 gene that cause autosomal recessive nonsyndromic hearing loss.  Hum Mutat . 1998;  11 387-394
• 41 Cohn E S, Kelley P M, Fowler T W. Clinical studies of families with hearing loss attributable to mutations in the connexin 26 gene (GJB2/DFNB1).  Pediatrics . 1999;  103 546-552
• 42 Denoyelle F, Marlin S, Weil D. Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling.  Lancet . 1999;  353 1298-1303
• 43 Mueller R F, Nehammer A, Middleton A. Congenital non-syndromal sensorineural hearing impairment due to connexin 26 gene mutations-molecular and audiological findings.  Int J Pediatr Otorhinolaryngol . 1999;  50 3-13
• 44 Liu X Z, Walsh J, Mburu P. Mutations in the myosin VIIA gene cause non-syndromic recessive deafness.  Nature Genet . 1997;  16 188-190
• 45 Weil D, Küssel P, Blanchard S. The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene.  Nature Genet . 1997;  16 191-193
• 46 Wang A, Liang Y, Fridell R A. Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3 Science .  1998;  280 1447-1451
• 47 Li X C, Everett L A, Lalwani A K. A mutation in PDS causes non-syndromic recessive deafness.  Nature Genet . 1998;  18 215-217
• 48 Yasunaga S, Grati M, Cohen-Salmon M. A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness.  Nature Genet . 1999;  21 363-369
• 49 Mustapha M, Weil D, Chardenoux S. An α-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual non-syndromic deafness, DFNB21.  Hum Mol Genet . 1999;  8 409-412
• 50 Estivill X, Govea N, Barceló A. Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment of aminoglycosides.  Am J Hum Genet . 1998;  62 27-35
• 51 Verhoeven K, Van Laer L, Kirschhofer K. Mutations in the human α-tectorin gene cause autosomal dominant non-syndromic hearing impairment.  Nature Genet . 1998;  19 60-62
• 52 Kubisch C, Schroeder B C, Friedrich T. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.  Cell . 1999;  96 437-446
• 53 Xia J-H, Liu C-Y, Tang B-S. Mutations in the gene encoding gap junction protein β-3 associated with autosomal dominant hearing impairment.  Nature Genet . 1999;  20 370-373
• 54 Liu X-Z, Xia X J, Xu L R. Mutations in connexin31 underlie recessive as well as dominant non-syndromic hearing loss.  Hum Mol Genet . 2000;  9 63-67
• 55 Liu X Z, Walsh J, Tamagawa Y. Autosomal dominant non-syndromic deafness caused by a mutation in the myosin VIIA gene.  Nature Genet . 1997;  17 268-269
• 56 Coyle B, Coffey R, Armour J AL. Pendred syndrome (goitre and sensorineural hearing loss) maps to chromosome 7 in the region containing the nonsyndromic deafness gene DFNB4.  Nature Genet . 1996;  12 421-423
• 57 Everett L A, Glaser B, Beck J C. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS).  Nature Genet . 1997;  17 411-422
• 58 Phelps P D, Coffey R A, Trembath R A. Radiological malformations of the ear in Pendred syndrome.  Clin Radiol . 1998;  53 268-273
• 59 Cremers C W, Admiraal R J, Huygen P L. Progressive hearing loss, hypoplasia of the cochlea and widened vestibular aqueducts are very common features in Pendred's syndrome.  Int J Pediatr Otorhinolaryngol . 1998;  45 113-23
• 60 Abe S, Usami S, Hoover D M. Fluctuating sensorineural hearing loss associated with enlarged vestibular aqueduct maps to 7q31, the region containing the Pendred gene.  Am J Med Genet . 1999;  82 322-328
• 61 Usami S, Abe S, Weston M D. Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused by PDS mutations.  Hum Genet . 1999;  104 188-192
• 62 Weber B P, Dillo W, Dietrich B. Pediatric cochlear implantation in cochlear malformations.  Am J Otol . 1998;  19 747-753
• 63 Cross N C, Stephens S D, Francis M. Computed tomography evaluation of the inner ear as a diagnostic, counselling and management strategy in patients with congenital sensorineural hearing impairment.  Clin Otolaryngol . 1999;  24 235-238