The inversa type of recessive dystrophic epidermolysis bullosa is caused by specific arginine and glycine substitutions in type VII collagen

Peter C van den Akker (1) , Jemima E Mellerio (2) , Anna E Martinez (3) , Lu Liu (2) , Rowdy Meijer (4) , Patricia Jc Dopping-Hepenstal (2) , Anthonie J van Essen (1) , Hans Scheffer (5) , Robert Mw Hofstra (6) , John A Mcgrath (2) , Marcel F Jonkman (1)

1 UMCG - University Medical Center Groningen [Groningen]
2 St John's Institute of Dermatology
3 GOSH - Great Ormond Street Hospital for Children [London]
4 Radboud University Medical Center [Nijmegen]
5 Department of Human Genetics [Nijmegen]
6 University of Groningen [Groningen]

Background The inversa type of recessive dystrophic epidermolysis bullosa (RDEB-I) is a rare variant of dystrophic epidermolysis bullosa, characterized by blistering in the body flexures, trunk, and mucosae. The cause of this specific distribution is unknown. So far, 20 COL7A1 genotypes have been described in RDEB-I and genotype-phenotype correlations have not been studied extensively. The aim of the study was to gain more insight into the pathophysiology of this intriguing RDEB-I phenotype. Methods We identified 20 Dutch and British RDEB-I patients and full genotypes in 18 of them. We reviewed the literature on RDEB-I genotypes and conducted an extensive genotype-phenotype correlation study for RDEB-I. Results All 20 patients had generalized blistering at birth and during early infancy. In most patients, the age of transition from generalized to inversa distribution was before the age of 4 years. We noted a spectrum of disease severity ranging from the mildest 'mucosal only' phenotype to the severest phenotype with limited acral involvement. The 29 genotypes of our RDEB-I patients and those reported in the literature revealed that RDEB-I is associated with specific recessive arginine and glycine substitutions in the triple-helix domain of type VII collagen. Discussion and conclusion Why these specific arginine and glycine substitutions cause the inversa distribution remains unknown. We could not identify clear differences in location and nature of substituting amino acids between these mutations and missense mutations causing other RDEB phenotypes. We hypothesize that the higher skin temperature in the affected areas plays an important role in the pathophysiology of RDEB-I.

Mots clés: Dermatology; Clinical genetics

Peter C van den Akker, Jemima E Mellerio, Anna E Martinez, Lu Liu, Rowdy Meijer, et al.. The inversa type of recessive dystrophic epidermolysis bullosa is caused by specific arginine and glycine substitutions in type VII collagen. Journal of Medical Genetics, 2010, 48 (3), pp.160. ⟨10.1136/jmg.2010.082230⟩. ⟨hal-00588661⟩