P160L mutation in the Ca(2+) ATPase 2A domain in a patient with severe Darier disease.
Darier disease (DD) is caused by mutations of the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca(2+)-ATPase isoform 2 (SERCA2). The mutations affect protein expression, degradation and activity. We report a patient with severe sporadic DD, who did not respond adequately to repeated courses of orally administered acitretin and isotretinoin. He was found to harbor the missense P160L mutation of the ATP2A2 gene in a heterozygous state in the A domain of SERCA2 and polymorphism in intron 18 (2741 + 54 G --> A). The A domain plays a key role in translocation of Ca(2+) from cytoplasm to endoplasmic reticulum lumen, thus establishing a low intracellular Ca(2+) concentration.
Department of Dermatovenereology, University Clinical Center, Ljubljana, Slovenia. aleksandar.godic@mf.uni-lj.si
Aleksandar
A
Godic
Damjan
D
Glavac
Branka
B
Korosec
Jovan
J
Miljković
Marko
M
Potocnik
Aleksej
A
Kansky
D000328:Adult; D001707:Biopsy, Needle; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D007644:Darier Disease / Q000235:genetics* / Q000473:pathology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D011379:Prognosis; D018570:Risk Assessment; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012720:Severity of Illness Index
D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D000252:Calcium-Transporting ATPases