The clinical features of Ehlers-Danlos syndrome type VIIB resulting from a base substitution at the splice acceptor site of intron 5 of the COL1A2 gene.

Abstract

The features of a 32 year old woman with Ehlers-Danlos syndrome type VIIB and affected members of her family, resulting from a mutation in one COL1A2 allele, were studied. Her dermal type I collagen contained a2(I) chains and mutant pN-a2(I) chains in which the amino-terminal propeptide remained attached to the a2(I) chain. She was heterozygous for an AG-AC mutation at the splice acceptor site of intron 5 of the COL1A2 gene. The mutation activated a cryptic AG splice acceptor site corresponding to positions + 14 and + 15 of exon 6 of the COL1A2 gene. In contrast to previous reports only five, rather than all 18, amino acids encoded by exon 6 were deleted in the proband. The deleted peptide removed the amino-proteinase cleavage site, but not the nearby lysine cross linking site in the amino-telopeptide of the a2(I) chain.She was born with bilateral hip dislocations, knee subluxations, and generalised joint hypermobility. Bilateral inguinal herniae and an umbilical hernia were present at birth. Facial features included a depressed nasal bridge with prominent paranasal folds. The skin was soft, moderately hyperelastic, and sagged over the face. Skin fragility and easy bruising were apparent from childhood. Skin wounds healed slowly and with broad, paper thin scars. Throughout her life, she had multiple fractures of the small bones of her hands and feet following moderate trauma.

The Ehlers–Danlos syndromes, rare types

“…At present, 49 patients from 36 families have been published (Table S1). The ages at the publication ranged from 2.5 months to 46 years (n = 35; Median age, 7.5 years of age) [Steinmann et al, ; Eyre et al, ; Cole et al, ; Viljoen et al, ; D'Alessio et al, ; Nicholls et al, ; Vasan et al, ; Chiodo et al, ; Pope et al, ; Carr et al, ; Ho et al, ; Lehmann et al, ; Byers et al, ; Giunta et al, ; Hudgins et al, ; Nicholls et al, ; Whitaker et al, ; Giovannucci Uzielli et al, ; Klaassens et al, ; Giunta and Steinmann, ; Hatamochi et al, ].…”

Mutations in TCF8 Cause Posterior Polymorphous Corneal Dystrophy and Ectopic Expression of COL4A3 by Corneal Endothelial Cells

“…It is estimated that as many as 20% of inguinal hernia patients have a positive family history (Tam 1990), pointing to a potential genetic etiology for this common condition. Inguinal hernias are also associated with several inherited connective tissue diseases like Ehlers-Danlos syndrome (Carr et al 1994) and primary joint hypermobility syndrome, which also includes features of Marfan syndrome, Elhers-Danlos syndrome, and osteogenesis imperfecta (Skoumal et al 2004). It has previously been proposed elswhere that defects in the level of col-…”

Clinical features, molecular results, and management of 12 individuals with the rare arthrochalasia Ehlers‐Danlos syndrome

“…Arthrochalasia EDS is a rare disorder with an unknown prevalence (Brady et al, ). To date, 42 patients with aEDS from 37 families have been published (Byers et al, ; Carr et al, ; Chiodo, Hockey, & Cole, ; Cole, Chan, Chambers, Walker, & Bateman, ; Cole, Evans, & Sillence, ; D'Alessio et al, ; Eyre, Shapiro, & Aldridge, ; Giovannucci Uzielli et al, ; C Giunta & Steinmann, ; C Giunta, Superti‐Furga, Spranger, Cole, & Steinmann, ; Hass & Hass, ; Hatamochi, Hamada, Yoshino, & Hashimoto, ; Ho et al, ; Hudgins, Drummond‐Borg, Atkinson, Schwarze, & Byers, ; Klaassens et al, ; Lehmann et al, ; Melis et al, ; a C. Nicholls et al, ; A. C. Nicholls et al, ; Pope et al, ; Vasan et al, ; Viljoen, Goldblatt, Thompson, & Beighton, ; Watson et al, ; D. Weil et al, , Weil et al, ; Dominique Weil, D'Alessio, Ramirez, & Eyre, ; Whitaker et al, ). Here we describe 12 individuals with aEDS from ten families, including follow‐up data on six patients and data on six newly diagnosed individuals in order to expand knowledge about clinical features, molecular diagnosis, and management.…”