Ehlers-Danlos Syndrome Caused by Biallelic TNXB Variants in Patients with Congenital Adrenal Hyperplasia.
PreventionGenetics, Marshfield, Wisconsin.
National Institutes of Health Clinical Center, Bethesda, Maryland.
Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland.
Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California.
National Institutes of Health, , National Institute on Aging, Baltimore, Maryland.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
- Published Article
Wiley (John Wiley & Sons)
- Publication Date
Sep 01, 2016
Some variants that cause autosomal-recessive congenital adrenal hyperplasia (CAH) also cause hypermobility type Ehlers-Danlos syndrome (EDS) due to the monoallelic presence of a chimera disrupting two flanking genes: CYP21A2, encoding 21-hydroxylase, necessary for cortisol and aldosterone biosynthesis, and TNXB, encoding tenascin-X, an extracellular matrix protein. Two types of CAH tenascin-X (CAH-X) chimeras have been described with a total deletion of CYP21A2 and characteristic TNXB variants. CAH-X CH-1 has a TNXB exon 35 120-bp deletion resulting in haploinsufficiency, and CAH-X CH-2 has a TNXB exon 40 c.12174C>G (p.Cys4058Trp) variant resulting in a dominant-negative effect. We present here three patients with biallelic CAH-X and identify a novel dominant-negative chimera termed CAH-X CH-3. Compared with monoallelic CAH-X, biallelic CAH-X results in a more severe phenotype with skin features characteristic of classical EDS. We present evidence for disrupted tenascin-X function and computational data linking the type of TNXB variant to disease severity.
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This record was last updated on 06/09/2018 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/27297501