Details

Autor(en) / Beteiligte

• Li, D.
• Ryu, E.
• Saeidian, A.H.
• Youssefian, L.
• Oliphant, E.
• Terry, S.F.
• Tong, P.L.
• Uitto, J.
• Haass, N.K.
• Li, Q.

Titel

GGCX mutations in a patient with overlapping pseudoxanthoma elasticum/cutis laxa‐like phenotype

Ist Teil von

• British journal of dermatology (1951), 2021-06, Vol.184 (6), p.1170-1174

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Summary Pseudoxanthoma elasticum (PXE) is a multisystem disorder characterized by ectopic mineralization of connective tissues with primary manifestations in the skin, eyes and the cardiovascular system. The classic forms of PXE are caused by mutations in the ABCC6 gene encoding the ABCC6 protein, expressed primarily in the liver. Cutis laxa (CL) manifests with loose and sagging skin with loss of recoil. In 2009 we investigated a 19‐year‐old patient with overlapping cutaneous features of PXE and CL, together with alpha thalassaemia. Genetic analysis failed to identify pathogenic mutations in ABCC6. More recently we developed a gene‐targeted panel of next‐generation sequencing technology. This panel has 29 genes, 22 of which, including ABCC6 and GGCX, are associated with ectopic mineralization phenotypes. Mutation analysis in the patient identified two heterozygous GGCX mutations: c.200_201delTT in exon 2 and c.763G>A, p.V255M in exon 7. The GGCX gene encodes a γ‐glutamyl carboxylase necessary for activation of blood coagulation factors in the liver. The p.V255M mutation was previously reported to result in reduced γ‐glutamyl carboxylase activity in vitro, while the c.200_201delTT mutation is novel. Previous studies reported that mutations in GGCX cause overlapping PXE/CL skin phenotypes in association with or without multiple vitamin K‐dependent coagulation factor deficiency. Our patient had loose redundant skin, moderate‐to‐severe angioid streaks and characteristic calcification of elastic structures in the mid dermis, consistent with PXE/CL overlap, but no coagulation abnormalities. Our studies expand the GGCX mutation landscape in patients with PXE‐like phenotypes. What is already known about this topic? Pseudoxanthoma elasticum (PXE) is caused in most cases by mutations in the ABCC6 gene. Combined PXE and cutis laxa (CL)‐like clinical findings have been encountered with vitamin K‐dependent coagulation factor deficiency frequently caused by GGCX mutations. GGCX encodes a γ‐glutamyl carboxylase necessary for activation of vitamin K‐dependent coagulation factors in the liver. What does this study add? This study reports a unique case with an overlapping PXE/CL‐like clinical phenotype with no evidence of a coagulation disorder. The patient carries compound heterozygous mutations in GGCX, adding to the mutation spectrum of GGCX‐associated phenotypes.