Absence of GJB2 gene mutations, the GJB6 deletion (GJB6-D13S1830) and four common mitochondrial mutations in nonsyndromic genetic hearing loss in a South African population

International Journal of Pediatric Otorhinolaryngology

Volumn 75, Issue 5, 2011, Pages 611-617

  Kabahuma, Rosemary I ^a,b   Ouyang, Xiaomei ^c   Du, Li Lin ^c   Yan, Denise ^c   Hutchin, Tim ^d   Ramsay, Michele ^a   Penn, Claire ^a   Liu, Xue Zhong ^c  

^a UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^b Polokwane/Mankweng Hospital Complex   (South Africa)

^c UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^d BIRMINGHAM CHILDREN S HOSPITAL   (United Kingdom)

Author keywords

GJB2; GJB6 D13S1830; Molecular diagnosis; MtDNA mutations; Non syndromic hearing loss; South African population

Indexed keywords

CONNEXIN 30; MITOCHONDRIAL DNA;

ADOLESCENT; ADULT; ARTICLE; CAUCASIAN; CHILD; CONTROLLED STUDY; FEMALE; GENE; GENE DELETION; GENE FREQUENCY; GENE MUTATION; GENETIC SCREENING; GJB2 GENE; HEARING LOSS; HUMAN; MAJOR CLINICAL STUDY; MALE; MITOCHONDRION; MULTIPLEX POLYMERASE CHAIN REACTION; POPULATION RESEARCH; PRESCHOOL CHILD; PREVALENCE; PRIORITY JOURNAL; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; SCHOOL CHILD; SINGLE STRAND CONFORMATION POLYMORPHISM; SOUTH AFRICA;

ADOLESCENT; AFRICA SOUTH OF THE SAHARA; AFRICAN CONTINENTAL ANCESTRY GROUP; AUDIOMETRY; CHILD; CHILD, PRESCHOOL; COHORT STUDIES; CONNEXINS; DNA, MITOCHONDRIAL; FEMALE; GENE DELETION; GENETIC PREDISPOSITION TO DISEASE; HEARING LOSS; HEARING LOSS, SENSORINEURAL; HEARING TESTS; HUMANS; INCIDENCE; MALE; MASS SCREENING; MUTATION; POLYMERASE CHAIN REACTION; POLYMORPHISM, RESTRICTION FRAGMENT LENGTH; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; YOUNG ADULT;

EID: 79954630324     PISSN: 01655876     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ijporl.2011.01.029     Document Type: Article

References (63)

1. Morton N.E. Genetic epidemiology of hearing impairment. Ann. N. Y. Acad. Sci. 1991, 630:16-31.
2. Newton V.E. Aetiology of bilateral sensori-neural hearing loss in young children. J. Laryngol. Otol. Suppl. 1985, 10:1-57.
3. Parving A. Aetiological diagnosis in hearing-impaired children-clinical value and application of a modern examination programme. Int. J. Pediatr. Otorhinolaryngol. 1984, 7:29-38.
4. Petit C., Levilliers J., Hardelin J.P. Molecular genetics of hearing loss. Annu. Rev. Genet. 2001, 35:589-646.
5. Rabionet R., Gasparini P., Estivill X. Molecular genetics of hearing impairment due to mutations in gap junction genes encoding beta connexins. Hum. Mutat. 2000, 16:190-202.
6. Fraser G.R. The Causes of Profound Deafness in Childhood: A Study of 3535 Individuals with Severe Hearing Loss Present at Birth or of Childhood Onset 1976, Johns Hopkins University Press, Baltimore.
7. Keats B.J., Berlin C.I. Genomics and hearing impairment. Genome Res. 1999, 9:7-16.
8. Konigsmark B.W. Hereditary deafness in man. N. Engl. J. Med. 1969, 281:827-832.
9. Resendes B.L., Williamson R.E., Morton C.C. At the speed of sound: gene discovery in the auditory system. Am. J. Hum. Genet. 2001, 69:923-935.
10. Steel K.P., Kros C.J. A genetic approach to understanding auditory function. Nat. Genet. 2001, 27:143-149.
11. G. Van Camp, R. Smith, Hereditary Hearing Loss. Available at / (accessed April 2010). http://hereditaryhearingloss.org/.
12. Cohn E.S., Kelley P.M. Clinical phenotype and mutations in connexin 26 (DFNB1/GJB2), the most common cause of childhood hearing loss. Am. J. Med. Genet. 1999, 89:130-136.
13. del Castillo I., Moreno-Pelayo M.A., Del Castillo F.J., Brownstein Z., Marlin S., Adina Q., et al. Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multicenter study. Am. J. Hum. Genet. 2003, 73:1452-1458.
14. Fuse Y., Doi K., Hasegawa T., Sugii A., Hibino H., Kubo T. Three novel connexin26 gene mutations in autosomal recessive non-syndromic deafness. Neuroreport 1999, 10:1853-1857.
15. Kelsell D.P., Dunlop J., Stevens H.P., Lench N.J., Liang J.N., Parry G., et al. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 1997, 387:80-83.
16. Pandya A., Arnos K.S., Xia X.J., Welch K.O., Blanton S.H., Friedman T.B., et al. Frequency and distribution of GJB2 (connexin 26) and GJB6 (connexin 30) mutations in a large North American repository of deaf probands. Genet. Med. 2003, 5:295-303.
17. Hamelmann C., Amedofu G.K., Albrecht K., Muntau B., Gelhaus B.A., Brobby G.W. Pattern of connexin 26 (GJB2) mutations causing sensorineural hearing impairment in Ghana. Hum. Mutat. 2001, 18:84-85.
18. Zelante L., Gasparini P., Estivill X., Melchionda S., D'Agruma L., Govea N., et al. 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.
19. Liu X.Z., Xia X.J., Ke X.M., Ouyang X.M., Du L.L., LiU Y.H., et al. The prevalence of connexin 26(GJB2) mutations in the Chinese population. Hum. Genet. 2002, 111:394-397.
20. Gasmelseed N.M., Schmidt M., Magzoub M.M., Macharia M., Elmustafa O.M., Ototo B., et al. Low frequency of deafness-associated GJB2 variants in Kenya and Sudan and novel GJB2 variants. Hum. Mutat. 2004, 23:206-207.
21. Grifa A., Wagner C.A., D'Ambrosio L., Melchionda S., Bernardi F., Lopez-Bigas N., et al. Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus. Nat. Genet. 1999, 23:16-18.
22. Prezant T.R., Agapian J.V., Bohlman M.C., Bu X., Oztas S., Qiu W.Q., et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat. Genet. 1993, 4:289-294.
23. del Castillo F.J., Rodriguez-Ballesteros M., Martin Y., Arellano B., Gallo-Terán J., Morales-Angulo C., et al. Heteroplasmy for the 1555A>G mutation in the mitochondrial 12S rRNA gene in six Spanish families with non-syndromic hearing loss. J. Med. Genet. 2003, 40:632-636.
24. Estivill X., Govea N., Barcelo F., Badenas C., Romero E., Moral L., et al. 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.
25. Hutchin T., Haworth I., Higashi K., Fischel-Ghodsian N., Stoneking M., Saha N., et al. A molecular basis for human hypersensitivity to aminoglycoside antibiotics. Nucleic Acids Res. 1993, 21:4174-4179.
26. Li R., Greinwald J.H., Yang L., Choo D.I., Wenstrup R.J., Guan X.M., et al. Molecular analysis of the mitochondrial 12S rRNA and tRNASer(UCN) genes in paediatric subjects with non-syndromic hearing loss. J. Med. Genet. 2004, 41:615-620.
27. Li X., Fischel-Ghodsian N., Schwartz F., Yan Q.F., Friedman R.A., Guan X.M., et al. Biochemical characterization of the mitochondrial tRNASer(UCN) T7511C mutation associated with nonsyndromic deafness. Nucleic Acids Res. 2004, 32:867-877.
28. Matthijs G., Claes S., Longo-Mbenza B., Cassiman J. Non-syndromic deafness associated with a mutation and a polymorphism in the mitochondrial 12S ribosomal RNA gene in a large Zairean pedigree. Eur. J. Hum. Genet. 1996, 4:46-51.
29. Pandya A., Xia X., Radnaabazar J., Batsuuri J., Dangaansuren B., Fischel-Ghodsian N., et al. Mutation in the mitochondrial 12S rRNA gene in two families from Mongolia with matrilineal aminoglycoside ototoxicity. J. Med. Genet. 1997, 34:169-172.
30. Young W.Y., Zhao L., Qian Y., Wang Q., Li N., Greinwald J.H., et al. Extremely low penetrance of hearing loss in four Chinese families with the mitochondrial 12S rRNA A1555G mutation. Biochem. Biophys. Res. Commun. 2005, 328:1244-1251.
31. Statistics South Africa. Census 2001: Primary tables Limpopo. Statistics South Africa, 2004.
32. Miller S.A., Dykes D.D., Polesky H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988, 16:1215.
33. Wu B.L., Kenna M., Lip V., Irons M., Platt O. Use of a multiplex PCR/sequencing strategy to detect both connexin 30 (GJB6) 342kb deletion and connexin 26 (GJB2) mutations in cases of childhood deafness. Am. J. Med. Genet. A 2003, 121A:102-108.
34. Pandya A., Xia X.J., Erdenetungalag R., Amendola M., Landa B., Radnaabazar J., et al. Heterogenous point mutations in the mitochondrial tRNA Ser(UCN) precursor coexisting with the A1555G mutation in deaf students from Mongolia. Am. J. Hum. Genet. 1999, 65:1803-1806.
35. Sue C.M., Tanji K., Hadjigeorgiou G., Andreu A.L., Nishino I., Krishna S., et al. Maternally inherited hearing loss in a large kindred with a novel T7511C mutation in the mitochondrial DNA tRNA(Ser(UCN)) gene. Neurology 1999, 52:1905-1908.
36. N.J. Van Warmelo, W.M.D. Phophi, I. Venda Law, Betrothal, Thakha, Wedding. Government Printer, Pretoria, 1948.
37. D. Coplan, Countries and Their Cultures. Available at (accessed June 2006). http://www.everyculture.com/Sa-Th/South-Africa.html.
38. Brobby G.W., Muller-Myhsok B., Horstmann R.D. Connexin 26 R143W mutation associated with recessive nonsyndromic sensorineural deafness in Africa. N. Engl. J. Med. 1998, 338:548-550.
39. Denoyelle F., Marlin S., Weil D., Moatti L., Chauvin P., Garabédian E.N., et al. 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.
40. Morell R.J., Kim H.J., Hood L.J., Goforth L., Friderici K., Fisher R., et al. Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness. N. Engl. J. Med. 1998, 339:1500-1505.
41. Ohtsuka A., Yuge I., Kimura S., Namba A., Abe S., Van Laer L., et al. GJB2 deafness gene shows a specific spectrum of mutations in Japan, including a frequent founder mutation. Hum. Genet. 2003, 112:329-333.
42. Van Camp G., Smith R.J. Maternally inherited hearing impairment. Clin. Genet. 2000, 57:409-414.
43. Yan D., Park H.J., Ouyang X.M., Pandya A., Doi K., Erdenetungalag R., et al. Evidence of a founder effect for the 235delC mutation of GJB2 (connexin 26) in east Asians. Hum. Genet. 2003, 114:44-50.
44. Gasparini P., Estivill X., Volpini V., Totaro A., Castellvi-Bel S., Govea N., et al. Linkage of DFNB1 to non-syndromic neurosensory autosomal-recessive deafness in Mediterranean families. Eur. J. Hum. Genet. 1997, 5:83-88.
45. Green G.E., Scott D.A., McDonald J.M., Woodworth G.G., Sheffield V.C., Smith R.J. Carrier rates in the midwestern United States for GJB2 mutations causing inherited deafness. JAMA 1999, 281:2211-2216.
46. Oliveira C.A., Alexandrino F., Abe-Sandes K., Silva W.A., Maciel-Guerra A.T., Magna L.A., et al. Frequency of the 35delG mutation in the GJB2 gene in samples of European Asian, and African Brazilians. Hum. Biol. 2004, 76:313-316.
47. Gasparini P., Rabionet R., Barbujani G., Melçhionda S., Petersen M., Brøndum-Nielsen K., et al. High carrier frequency of the 35delG deafness mutation in European populations Genetic Analysis Consortium of GJB2 35delG. Eur. J. Hum. Genet. 2000, 8:19-23.
48. Simsek M., Al-Wardy N., Al-Khayat A., Shanmugakonar M., Al-Bulushi T., Khabory Al-M., et al. Absence of deafness-associated connexin-26 (GJB2) gene mutations in the Omani population. Hum. Mutat. 2001, 18:545-546.
49. Gualandi E., Ravani A., Berto A., Burdo S., Trevisi P., Ferlini A., et al. Occurrence of del(GIB6-D13S1830) mutation in Italian non-syndromic hearing loss patients carrying a single GJB2 mutated allele. Acta Otolaryngol. Suppl. 2004, 29-34.
50. Bolz H., Schade G., Ehmer S., Kothe C., Hess M., Gal A. Phenotypic variability of non-syndromic hearing loss in patients heterozygous for both c.35delG of GJB2 and the 342-kb deletion involving GJB6. Hear. Res. 2004, 188:42-46.
51. Gunther B., Steiner A., Nekahm-Heis D., Albegger K., Zorowka P., Utermann G., et al. The 342-kb deletion in GJB6 is not present in patients with non-syndromic hearing loss from Austria. Hum. Mutat. 2003, 22:180.
52. Tekin M., Duman T., Bogoclu G., Incesulu A., Comak E., Ilhan I., et al. Spectrum of GJB2 mutations in Turkey comprises both Caucasian and Oriental variants: roles of parental consanguinity and assortative mating. Hum. Mutat. 2003, 21:552-553.
53. Uyguner O., Emiroglu M., Uzumcu A., Hafiz G., Ghanbari A., Baserer N., et al. Frequencies of gap- and tight-junction mutations in Turkish families with autosomal-recessive non-syndromic hearing loss. Clin. Genet. 2003, 64:65-69.
54. Samanich J., Lowes C., Burk R., Shanske S., Lu J., Shanske A., et al. Mutations in GJB2 GJB6, and mitochondrial DNA are rare in African American and Caribbean Hispanic individuals with hearing impairment. Am. J. Med. Genet. A 2007, 143A:830-838.
55. Pallares-Ruiz N., Blanchet P., Mondain M., Claustres M., Roux A.F. A large deletion including most of GJB6 in recessive non syndromic deafness: a digenic effect?. Eur J. Hum. Genet. 2002, 1072-1076.
56. Fischel-Ghodsian N. Mitochondrial deafness mutations reviewed. Hum. Mutat. 1999, 13:261-270.
57. Jacobs H.T. Mitochondrial deafness. Ann. Med. 1997, 29:483-491.
58. Bravo O., Ballana E., Estivill X. Cochlear alterations in deaf and unaffected subjects carrying the deafness-associated A1555G mutation in the mitochondrial 12S rRNA gene. Biochem. Biophys. Res. Commun. 2006, 344:511-516.
59. Tang H.Y., Hutcheson E., Neill S., Drummond-Borg M., Speer M., Alford R.L. Genetic susceptibility to aminoglycoside ototoxicity: how many are at risk?. Genet. Med. 2002, 4:336-345.
60. Gravina L.P., Foncuberta M.E., Estrada R.C., Barreiro C., Chertkoff L. Carrier frequency of the 35delG and A1555G deafness mutations in the Argentinean population Impact on the newborn hearing screening. Int. J. Pediatr. Otorhinolaryngol. 2007, 71:639-643.
61. Usami S., Abe S., Akita J., Namba A., Shinkawa H., Ishii M., et al. Prevalence of mitochondrial gene mutations among hearing impaired patients. J. Med. Genet. 2000, 37:38-40.
62. Bardien S., Human H., Harris T., Hefke G., Veikondis R., Schaaf H.S., et al. A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness. BMC Med. Genet. 2009, 10:2.
63. Human H., Lombard D., de Jong G., Bardien S. A South African family with the mitochondrial A1555G mutation on haplogroup L0d. Biochem. Biophys. Res. Commun. 2009, 382:390-394.