Hallopeau–Siemens dystrophic epidermolysis bullosa due to homozygous 5818delC mutation in the COL7A gene

Abstract

Epidermolysis bullosa (EB) is a group of inherited mechanobullous skin disease. The dystrophic EB (DEB), one subtype of EB, is inherited in an autosomal dominant DEB or in an autosomal recessive (RDEB). DEB is caused by mutations in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils. Over 300 pathogenic mutations have been detected within COL7A in DEB. Patients with the Hallopeau-Siemens type (HS-RDEB), most severe form of DEB, frequently have premature termination codon (PTC) mutations on both alleles. PTC mutations on both alleles result in depleted mRNA and α1 helix, and failure to form the triple helix structure characteristic of type VII collagen. As patients with HS-RDEB usually have a pair of heterozygous PTC mutations, there have been rarely reported homozygous ones in HS-RDEB. We report the first case of HS-RDEB homozygous PTC mutations of 5818delC in both COL7A1 alleles. This case report suggests the positional effect of PTC mutations and vigilance against early infantile death in EB including HS-RDEB.

Recessive dystrophic epidermolysis bullosa (RDEB) complicated by secondary hepatic amyloidosis

“…AA amyloidosis occurs in chronic inflammatory diseases, where serum amyloid A protein concentration can increase greater than 2000 mg/L during the acute-phase response. 2 …”

“…Phenytoin is reported to be effective by inhibiting the synthesis and secretion of collagenase from dermal fibroblasts, and has been shown to increase tolerance against trauma. 2 Phenytoin may rarely cause hepatotoxicity, occurring in less than 1% of patients, usually within the first 6 weeks of treatment. 7 It has been associated with amyloidosis in 1 case report, with a 55-year-old man developing renal amyloidosis with a monoclonal gammopathy, without coexisting multiple myeloma or lymphoproliferative disorders.…”

“…Generalized severe recessive dystrophic EB (RDEB) is characterized by large, flaccid bullae present at birth with healing atrophic scars. 2 RDEB is associated with a high mortality and morbidity.…”

Genetic analysis and prenatal diagnosis of recessive dystrophic epidermolysis bullosa caused by compound heterozygous variants of the COL7A1 gene in a Chinese family

“…This disorder comes in two forms based on the pattern of inheritance: autosomal dominant DEB (DDEB; OMIM: 131750) and autosomal recessive DEB (RDEB; OMIM: 226600). The latter form is more severe; RDEB patients typically present with systemic blistering/scarring of the skin and mucous membranes, as well as defects in other organs (2)(3)(4).…”

Apparent Missense Variant in COL7A1 Causes a Severe Form of Recessive Dystrophic Epidermolysis Bullosa via Effects on Splicing

“…The phenotype ranges from very mild (isolated nail dystrophy or localized blistering only) to very severe (generalized blistering and failure to thrive). Autosomal recessive DEB (RDEB) is the most severe subtype of DEB, formerly known as Hallopeau-Siemens type (RDEB-HS), in which patients present with generalized lesions; scarring of the hands and feet, leading to fusion of the digits; and severe mucosal involvement ( 4 , 5 ).…”