GJB6 (Connexin 30) Sequencing for Hidrotic Ectodermal Dysplasia 2 Test Details
Hidrotic Ectodermal Dysplasia 2 (HED2), also referred to as Clouston syndrome, is characterized by hypotrichosis (sparse hair), dysplastic nails, and palmoplantar hyperkeratosis. Other features can include hyperpigmentation of the skin particularly over joints (such as knuckles or knees) and clubbing of the fingers. Unlike other ectodermal dysplasias, sweating and tooth development are normal. Individuals with HED2 often have hair that is thin, slow-growing, and lightly pigmented. Typically onset of sparse and brittle hair begins in infancy with progressive hair loss over time. Eyebrows and eyelashes may also be sparse or missing. Axillary and pubic hair is also impacted and may be sparse or absent. Onset of white or milky nails often begins in childhood and also progresses over time. Childhood onset of hyperkeratosis can also occur with progression of severity with age. High variation of clinical features can be seen between individuals, even within the same family.Read More...
Hidrotic ectodermal dysplasia 2 is inherited in an autosomal dominant manner. There are four common pathogenic variants identified in individuals with HED2. The variants are: p.Gly11Arg, p.Val37Glu, p.Asp50Asn, and p.Ala88Val. Some of these variants are more common in certain populations. (Lamartine 2000, Smith 2002, Zhang 2003, Baris 2008). De novo cases have been reported (Smith 2002).Less
|GJB6||Gap Junction Protein, Beta-6||604418||13q12|
Sequencing for the GJB6 gene would be indicated for individual with clinical features associated with hidrotic ectodermal dysplasia 2 (HED2) including: hypotrichosis (sparse hair), dysplastic nails (slow growing, short, thick), palmoplantar keratoderma (overgrowth of skin on the palms the hands and soles of the feet). All pathogenic variants have been identified in exon 3 of the GJB6 gene; therefore, the testing of other exons in this gene is not indicated.
This test is performed by Sanger sequencing of the coding regions and splice sites of exon 3 of the GJB6 gene. This test does not detect large deletions or variants in non-coding regions that could affect gene expression.
Analytical and Clinical Sensitivity
This test is greater than 99.9% accurate in detecting variants in the sequence analyzed. Approximately 100% of individuals with a clinical diagnosis of Hidrotic Ectodermal Dysplasia 2 have one of the common four point mutations in the GJB6 gene. The presence of other variants in this gene related to HED2 is unknown.