Under‐recognition of acral peeling skin syndrome: 59 new cases with 15 novel mutations. (20th October 2014)

• Record Type: Journal Article
• Authors: Szczecinska, W.; Nesteruk, D.; Wertheim‐Tysarowska, K.; Greenblatt, D.T.; Baty, D.; Browne, F.; Liu, L.; Ozoemena, L.; Terron‐Kwiatkowski, A.; McGrath, J.A.; Mellerio, J.E.; Morton, J.; Woźniak, K.; Kowalewski, C.; Has, C.; Moss, C.
• Is Part Of: British journal of dermatology. Volume 171:Number 5(2014:Nov.)
• Page Start: 1206
• Page End: 1210
• Publication Date: 2014-10-20
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.12964
• Languages: English
• ISSNs: 0007-0963

Abstract

<abstract abstract-type="main" id="bjd12964-abs-0001"> <title>Summary</title> <sec id="bjd12964-sec-0001" sec-type="section"> <title>Background</title> <p>Acral peeling skin syndrome (APSS) is a rare skin fragility disorder usually caused by mutations in the transglutaminase 5 gene (<italic>TGM5</italic>).</p> </sec> <sec id="bjd12964-sec-0002" sec-type="section"> <title>Methods</title> <p>We investigated the mutation spectrum of APSS in the U.K., Germany and Poland.</p> </sec> <sec id="bjd12964-sec-0003" sec-type="section"> <title>Results</title> <p>We identified 59 children with APSS from 52 families. The phenotype was readily recognizable, with some variation in severity both within and between families. Most cases had been misdiagnosed as the localized form of epidermolysis bullosa simplex (EBS‐loc). Eighteen different <italic>TGM5</italic> mutations were identified, 15 of which were novel. Eight mutations were unique to a single family, nine each occurred in two families, while the common p.Gly113Cys mutation linked to a second missense variant p.Thr109Met occurred in 47 of the 52 families and was homozygous in 28. Most patients were of nonconsanguineous white European origin.</p> </sec> <sec id="bjd12964-sec-0004" sec-type="section"> <title>Conclusions</title> <p>We propose that APSS is under‐reported and widely misdiagnosed as EBS‐loc, with significant counselling implications as APSS is autosomal recessive while EBS‐loc is dominant. We recommend screening for <italic>TGM5</italic> mutations when EBS‐loc is suspected but not confirmed by mutations in <italic>KRT5</italic> or <italic>KRT14</italic>. Our report trebles the number of known <italic>TGM5</italic> mutations. It provides further evidence that p.Gly113Cys is a founder mutation in the European population. This is consistent with the striking ethnic distribution of APSS in U.K., where the majority of patients are of nonconsanguineous white European origin, in contrast to the pattern of other recessive skin disorders.</p> </sec> </abstract>