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Under-recognition of acral peeling skin syndrome: 59 new cases with 15 novel mutations
- Source :
- The British journal of dermatology. 171(5)
- Publication Year :
- 2014
-
Abstract
- Summary Background Acral peeling skin syndrome (APSS) is a rare skin fragility disorder usually caused by mutations in the transglutaminase 5 gene (TGM5). Methods We investigated the mutation spectrum of APSS in the U.K., Germany and Poland. Results 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 TGM5 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. Conclusions 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 TGM5 mutations when EBS-loc is suspected but not confirmed by mutations in KRT5 or KRT14. Our report trebles the number of known TGM5 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.
- Subjects :
- Heterozygote
Dermatology
medicine.disease_cause
Skin Diseases
Diagnosis, Differential
Epidermolysis bullosa simplex
Germany
medicine
Missense mutation
Humans
Genetic Testing
Child
Gene
Acral peeling skin syndrome
Genetics
Mutation
Transglutaminases
business.industry
Homozygote
Keratin-14
medicine.disease
Phenotype
Founder Effect
United Kingdom
White (mutation)
Epidermolysis Bullosa Simplex
Keratin-5
Poland
business
Pigmentation Disorders
Transglutaminase 5
Dermatitis, Exfoliative
Subjects
Details
- ISSN :
- 13652133
- Volume :
- 171
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- The British journal of dermatology
- Accession number :
- edsair.doi.dedup.....4bcb68d30d86a7919962702f9e9cb811