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Case Reports
. 2025 May;13(5):e2474.
doi: 10.1002/mgg3.2474.

A new syndromic case of hearing loss and ectodermal anomalies associated with a recurrent missense variation in GJB6 gene

Badreddine Elmakhzen  1   2 , Paul Rollier  1   3 , Clémence Saillard  4 , Benoit Godey  5 , Cédric Le Marechal  6 , Paul Gueguen  6 , Isabelle Fajardy  7 , Sylvie Odent  1   3 , Laurent Pasquier  8
Affiliations
Case Reports

A new syndromic case of hearing loss and ectodermal anomalies associated with a recurrent missense variation in GJB6 gene

Badreddine Elmakhzen et al. Mol Genet Genomic Med. 2025 May.

Abstract

GJB2 and GJB6 variants, encoding Cx26 and Cx30 respectively, are the most frequently involved genes commonly contributing to hereditary hearing loss either isolated or in combination with skin abnormalities. GJB6 variations are classically associated with two distinct conditions: non-syndromic hearing loss and hidrotic ectodermal dysplasia, type Clouston, the latter typically not involving deafness.

Method: Whole genome sequencing (WGS) was used to find genetic variants after clinical features of a 13-year-old female patient were recorded.

Results: In this report, we describe the association of congenital hearing loss and ectodermal anomalies (palmoplantar keratoderma, knuckle pads, and nail dystrophy) in a female with the ENST00000647029.1 (GJB6): c.175G>A (p.(Gly59Arg)) GJB6 variant. As a result, we report on the third case of individuals showing this same missense variant and syndromic hearing loss.

Conclusion: This study underscores the overlapping phenotypes observed in patients with the p.Gly59Arg variant in the GJB6 gene. The findings suggest a continuum of phenotypic presentations for this variant, with the key clinical features being the combination of congenital hearing loss and hyperkeratosis.

Keywords: GJB6 gene; palmoplantar keratoderma; syndromic hearing loss.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Skin clinical features. (a and b) Hyperkeratotic lesions on the backs of the toes and the hands (arrow). (c) Palmar keratoderma (arrow). (d) Pigmented patches of the right upper hemi thorax and right arm with non‐inflammatory pigmented melanocytic lesions.
FIGURE 2
FIGURE 2
Height, weight head and circumference charts showing tall stature and mild macrocephaly.
See this image and copyright information in PMC

References

    1. Alexandrino, F. , Sartorato, E. L. , Marques‐de‐Faria, A. P. , & Steiner, C. E. (2005). G59S mutation in theGJB2 (connexin 26) gene in a patient with Bart‐Pumphrey syndrome. American Journal of Medical Genetics, 136A(3), 282–284. - PubMed
    1. Avshalumova, L. , Fabrikant, J. , & Koriakos, A. (2014). Overview of skin diseases linked to connexin gene mutations. International Journal of Dermatology, 53(2), 192–205. - PubMed
    1. Berger, A. C. , Kelly, J. J. , Lajoie, P. , Shao, Q. , & Laird, D. W. (2014). Mutations in Cx30 that are linked to skin disease and non‐syndromic hearing loss exhibit several distinct cellular pathologies. Journal of Cell Science, 127(8), 1751–1764. - PubMed
    1. Delmar, M. , Laird, D. W. , Naus, C. C. , Nielsen, M. S. , Verselis, V. K. , & White, T. W. (2018). Connexins and disease. Cold Spring Harbor Perspectives in Biology, 10(9), a029348. - PMC - PubMed
    1. Duzkale, N. , Aygar, G. T. , Keseroglu, K. , Mutlu, M. , & Ugur, M. B. (2022). Causal variants of the GJB6 gene are associated with hearing loss and skin manifestations: A case report from Turkey. International Journal of Dermatology and Venereology., 5(3), 166–168.

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