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ADAMTSL2 gene variant in patients with features of autosomal dominant connective tissue disorders
Steinle, Jacob Hossain, Waheeda A. Lovell, Scott Veatch, Olivia J. Butler, Merlin G.
Steinle, Jacob
Hossain, Waheeda A.
Lovell, Scott
Veatch, Olivia J.
Butler, Merlin G.
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Abstract
Ehlers-Danlos syndrome (EDS) consists of a heterogeneous group of genetically inherited connective tissue disorders. A family with three affected members over two generations with features of Dermatosparaxic EDS (dEDS) autosomal dominant transmission was reported by Desai et al. and having a heterozygous nonsynonymous missense variant of ADAMTSL2 (c.1261G > A; p. Gly421Ser). Variation in this gene is also reported to cause autosomal recessive geleophysic dysplasia. We report five unrelated patients with the Gly421Ser variant identified from a large series of patients presenting with features of connective tissue disorders, each with a positive family history consistent with autosomal dominant transmission. Clinical features of a connective tissue disorder included generalized joint hypermobility and pain with fragility of internal and external tissues including of skin, dura, and arteries. Overall, our analyses including bioinformatics, protein modeling, and gene-protein interactions with the cases described would add evidence for the Gly421Ser variant in ADAMTSL2 as causative for variable expressivity of autosomal dominant connective tissue disorders.
Description
This is the peer reviewed version of the following article: Steinle, J, Hossain, WA, Lovell, S, Veatch, OJ, Butler, MG. ADAMTSL2 gene variant in patients with features of autosomal dominant connective tissue disorders. Am J Med Genet Part A. 2021; 185A: 743– 752. https://doi.org/10.1002/ajmg.a.62030, which has been published in final form at https://doi.org/10.1002/ajmg.a.62030. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
Date
2020-12-27
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Wiley
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Keywords
ADAMTSL2 gene, Autosomal dominant transmission, Ehlers-Danlos syndrome (EDS), Hypermobility and tissue fragility, Next-generation sequencing (NGS), Protein modeling
Citation
Steinle, J, Hossain, WA, Lovell, S, Veatch, OJ, Butler, MG. ADAMTSL2 gene variant in patients with features of autosomal dominant connective tissue disorders. Am J Med Genet Part A. 2021; 185A: 743– 752. https://doi.org/10.1002/ajmg.a.62030