Novel mutations in Darier disease and association to self-reported disease severity

被引:16
作者
Leong, Ivone U. S. [1 ]
Stuckey, Alexander [2 ]
Ahanian, Tara [1 ,3 ]
Cederlof, Martin [4 ]
Wikstrom, Jakob D. [1 ,3 ]
机构
[1] Karolinska Inst, Dept Med Solna, Dermatol & Venereol Unit, Stockholm, Sweden
[2] Royal Inst Technol, Sci Life Lab, Sch Biotechnol, Div Gene Technol, Stockholm, Sweden
[3] Karolinska Univ Hosp, Dermato Venereol Clin, Stockholm, Sweden
[4] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden
来源
PLOS ONE | 2017年 / 12卷 / 10期
基金
瑞典研究理事会;
关键词
ATP2A2; MUTATIONS; HAILEY-HAILEY; PREDICTION; DISORDERS; SPECTRUM; FEATURES; DATABASE; MUTANTS; SERCA2; PUMP;
D O I
10.1371/journal.pone.0186356
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Darier disease is a rare and severe autosomal dominant skin disease characterised by malodorous keratotic papules in seborrheic areas of the skin. Darier disease affects up to 1 in 30 000 people and is caused by mutations in the ATP2A2 gene, which encodes to the sarco/endoplasmic reticulum calcium-ATPase isoform 2 that pumps calcium into the endoplasmic reticulum. Although many ATP2A2 variants have been described, it is not known if genotype correlates with phenotype, which could be important for prognosis and treatment. This is the first study to use whole exome sequencing to screen the ATP2A2 gene in a cohort of 28 clinically diagnosed Darier disease patients. Twenty-one different disease causing variants were identified and 15 of these were novel. Sixteen of the 21 variants were predicted to be pathogenic using in silico prediction programs. There were seven missense, four intronic/splice-sites, three frameshifts, two in-frame deletions, four nonsense and one synonymous mutations. This study also found ten patients who harbour more than one ATP2A2 variant. The phenotype of the patient cohort was assessed by photography and by patient questionnaires. The genotype-phenotype association was examined for all variants in relation to the patient's disease severity score, and no correlation could be established.
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页数:15
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