Heterozygous p.Asp50Asn mutation in the GJB2 gene in two Cameroonian patients with keratitis-ichthyosis-deafness (KID) syndrome

BMC Medical Genetics

Geneviève Bengono Toure²  Collet Dandara³  Jason Bosch³  Jean Jacques N Noubiap²  Ambroise Wonkam¹ 

[1] Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa;Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon;Division of Human Genetics, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

关键词: Cameroon;    Africa;    p.Asp50Asn mutation;    GJB2 gene;    KID syndrome;   

Others  :  1122678
DOI  :  10.1186/1471-2350-14-81

 received in 2013-02-21, accepted in 2013-08-07,  发布年份 2013

【 摘 要 】

Background

Keratitis-Ichthyosis-Deafness (KID) syndrome (OMIM 148210) is a congenital ectodermal defect that consists of an atypical ichthyosiform erythroderma associated with congenital sensorineural deafness. KID appears to be genetically heterogeneous and most cases are caused by GJB2 mutations. Mutations in African patients have been rarely described.

Case presentation

We report on two unrelated Cameroonian individuals affected with sporadic KID, presenting with the classic phenotypic triad. The two patients were heterozygous for the most frequent p.Asp50Asn mutation. This first report in patients from sub-Saharan African origin supports the hypothesis that the occurrence of KID due to p.Asp50Asn mutation in GJB2 seems not to be population specific.

Conclusions

Our finding has implication in medical genetic practice, specifically in the molecular diagnosis of KID in Africans. These cases also reveal and emphasize the urgent need to develop appropriate policies to care for patients with rare/orphan diseases in Sub-Saharan Africa, as many of these cases become more and more recognizable.

【 授权许可】

   
2013 Wonkam et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Genetics Home Reference, Keratitis-ichthyosis-deafness syndrome. (Reviewed November 2012)http://ghr.nlm.nih.gov/condition/keratitis-ichthyosis-deafness-syndrome webcite
• [2]Evans WH, Martin PE: Gap junctions: structure and function. Mol Membr Biol 2002, 19:121-136.
• [3]Pfenniger A, Wohlwend A, Kwak BR: Mutations in connexin genes and disease. Eur J Clin Invest 2011, 41:103-116.
• [4]Skinner BA, Greist MC, Norins AL: The keratitis, ichthyosis, and deafness (KID) syndrome. Arch Dermatol 1981, 117:285-289.
• [5]Richard G, Rouan F, Willoughby CE, Brown N, Chung P, Ryynänen M, Jabs EW, Bale SJ, DiGiovanna JJ, Uitto J, Russell L: Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome. Am J Hum Genet 2002, 70:1341-1348.
• [6]Jan AY, Amin S, Ratajczak P, Richard G, Sybert VP: Genetic heterogeneity of KID syndrome: identification of a CX30 Gene (GJB6) mutation in a patient with KID syndrome and congenital atrichia. J Invest Dermatol 2004, 122:1108-1113.
• [7]Jonard L, Feldmann D, Parsy C, Freitag S, Sinico M, Koval C, Grati M, Couderc R, Denoyelle F, Bodemer C, Marlin S, Hadj-Rabia S: A familial case of keratitis-ichthyosis-deafness (KID) syndrome with the GJB2 mutation G45E. Eur J Med Genet 2008, 51:35-43.
• [8]Maintz L, Betz RC, Allam JP, Wenzel J, Jaksche A, Friedrichs N, Bieber T, Novak N: Keratitis-ichthyosis-deafness syndrome in association with follicular occlusion triad. Eur J Dermatol 2005, 15:347-352.
• [9]Wonkam A, Noubiap JJ, Djomou F, Fieggen K, Njock R, Toure GB: Etiology of childhood hearing loss in Cameroon (sub-Saharan Africa). Eur J Med Genet 2013, 56:20-25.
• [10]Liu XZ, Xia XJ, Ke XM, Ouyang XM, Du LL, Liu YH, Angeli S, Telischi FF, Nance WE, Balkany T, Xu LR: The prevalence of connexin 26 (GJB2) mutations in the Chinese population. Hum Genet 2002, 111:394-397.
• [11]Pandya A, Arnos KS, Xia XJ, Welch KO, Blanton SH, Friedman TB, Garcia Sanchez G, Liu MDXZ, Morell R, Nance WE: 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.
• [12]Kabahuma RI, Ouyang X, Du LL, Yan D, Hutchin T, Ramsay M, Penn C, Liu XZ: 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. Int J Pediatr Otorhinolaryngol 2011, 75:611-617.
• [13]Richard G: Connexin disorders of the skin. Clin Dermatol 2005, 23:23-32.
• [14]Lazic T, Li Q, Frank M, Uitto J, Zhou LH: Extending the phenotypic spectrum of keratitis-ichthyosis-deafness syndrome: report of a patient with GJB2 (G12R) Connexin 26 mutation and unusual clinical findings. Pediatr Dermatol 2012, 29:349-357.
• [15]Todt I, Mazereeuw-Hautier J, Binder B, Willems PJ: Dandy-Walker malformation in patients with KID syndrome associated with a heterozygote mutation (p.Asp50Asn) in the GJB2 gene encoding connexin 26. Clin Genet 2009, 76:404-408.
• [16]Mazereeuw-Hautier J, Bitoun E, Chevrant-Breton J, Man SY, Bodemer C, Prins C, Antille C, Saurat JH, Atherton D, Harper JI, Kelsell DP, Hovnanian A: Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients. Br J Dermatol 2007, 156:1015-1019.
• [17]Iossa S, Marciano E, Franzé A: GJB2 gene mutations in syndromic skin disorders with sensorineural hearing loss. Curr Genomics 2011, 12:475-785.
• [18]Zong WX, Thompson CB: Necrotic death as a cell fate. Genes Dev 2006, 20:1-15.
• [19]de Zwart-Storm EA, Rosa RF, Martin PE, Foelster-Holst R, Frank J, Bau AE, Zen PR, Graziadio C, Paskulin GA, Kamps MA, van Geel M, van Steensel MA: Molecular analysis of connexin26 asparagine14 mutations associated with syndromic skin phenotypes. Exp Dermatol 2011, 20:408-412.
• [20]Barker EJ, Briggs RJ: Cochlear implantation in children with keratitis-ichthyosis-deafness (KID) syndrome: outcomes in three cases. Cochlear Implants Int 2009, 10:166-173.