Author/Editor		Godić, Aleksander
Title		Molekularnogenetska analiza Darierjeve bolezni v slovenski populaciji
Type		monografija
Place		Ljubljana
Publisher		Univerza v Ljubljani, Medicinska fakulteta
Publication year		2004
Volume		str. 77
Language		slo
Abstract		Introduction Darier disease (follicular dyskeratosis, DD) is an autosomal dominant disease, caused by mutations of the ATP2A2 gene. It is characterized by hyperkeratotic papules and plaques, primarily in seborrheic areas. Involvement of nails, oral mucous membrane, and neuropsychiatric abnormalities may also be present. Materials and methods We examined 28 Slovenian DD patients ( ( 0 males and 18 females) and 2S refatives. They belonged to 8 families, 13 of them were islolated cases with no data on DD in their families. We included 64 healthy adults in a control group. We extracted DNA from peripheral blood leukocytes, amplified exons of the ATP2A2 gene with flanking intron boundaries and screened for mutations by single stranded conformational analysis (SSCA). We subsequently sequenced bands which showed abnormal electrophoretic mobility detected by SSCA. We detected a number of dyskeratotic cells in an observed reference space in a sample of DD histological sections with the method of morphometrical analysis. Results and discussion So far, 120 ATP2A2 family/patient specific mutations were described. According to the published data on DD, mutations were detected in 50-70% of patients; in our study we found mutations in one half of families. We identified 7 different mutations in 4 families and in 4 sporadic patients, 4 are new (AS 16P, RSS9G, 464-6de16, 1762-6del 18). The P 160L mutation was detected in a patient with severe disease. It affects the A-domain of the calcium pump, which plays a key role in translocation of Ca2+ from cytoplasm to a lumen of endoplasmic reticulum.
Descriptors		KERATOSIS FOLLICULARIS EXONS MUTATION PEDIGREE POLYMERASE CHAIN REACTION BASE SEQUENCE POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL SLOVENIA