title: A family with atypical Hailey Hailey disease--is there more to the underlying genetics than ATP2C1?
abstract: The autosomal dominant Hailey Hailey disease (HHD) is caused by mutations in the ATP2C1 gene encoding for human secretory pathway Ca2+/Mn2+ ATPase protein (hSPCA1) in the Golgi apparatus. Clinically, HHD presents with erosions and hyperkeratosis predominantly in the intertrigines. Here we report an exome next generation sequencing (NGS) based analysis of ATPase genes in a Greek family with 3 HHD patients presenting with clinically atypical lesions mainly localized on the neck and shoulders. By NGS of one HHD-patient and in silico SNP calling and SNP filtering we identified a SNP in the expected ATP2C1 gene and SNPs in further ATPase genes. Verification in all 3 affected family members revealed a heterozygous frameshift deletion at position 2355_2358 in exon 24 of ATP2C1 in all three patients. 7 additional SNPs in 4 ATPase genes (ATP9B, ATP11A, ATP2B3 and ATP13A5) were identified. The SNPs rs138177421 in the ATP9B gene and rs2280268 in the ATP13A5 gene were detected in all 3 affected, but not in 2 non affected family members. The SNPs in the ATP2B3 and ATP11A gene as well as further SNPs in the ATP13A5 gene could not be confirmed in all affected family members. One may speculate that besides the level of functional hSPCA1 protein, levels of other ATPase proteins may influence expressivity of the disease and might also contribute, as in this case, to atypical presentations.
authors.affiliation: Department of Dermatology, Allergology and Venerology, University of Luebeck, Luebeck, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: van Beek
authors.affiliation: 2nd Dermatology Department, Aristotle University School of Medicine, Papageorgiou General Hospital, Thessaloniki, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Patsatsi
authors.affiliation: Department of Dermatology, Allergology and Venerology, University of Luebeck, Luebeck, Germany.
authors.forename: Yask
authors.initials: Y
authors.lastname: Gupta
authors.affiliation: Department of Dermatology, Allergology and Venerology, University of Luebeck, Luebeck, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Möller
authors.affiliation: Department of Dermatology, Allergology and Venerology, University of Luebeck, Luebeck, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Freitag
authors.affiliation: Department of Dermatology, Allergology and Venerology, University of Luebeck, Luebeck, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lemcke
authors.affiliation: Department of Dermatology, Allergology and Venerology, University of Luebeck, Luebeck, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Recke
authors.affiliation: Department of Dermatology, Allergology and Venerology, University of Luebeck, Luebeck, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Zillikens
authors.affiliation: Department of Dermatology, Allergology and Venerology, University of Luebeck, Luebeck, Germany.
authors.forename: Enno
authors.initials: E
authors.lastname: Schmidt
authors.affiliation: Department of Dermatology, Allergology and Venerology, University of Luebeck, Luebeck, Germany.
authors.forename: Saleh
authors.initials: S
authors.lastname: Ibrahim
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000368:Aged; D001483:Base Sequence; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D005091:Exons; D015870:Gene Expression; D006115:Greece; D006579:Heterozygote; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016506:Pemphigus, Benign Familial / Q000235:genetics* / Q000473:pathology; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012867:Skin / Q000378:metabolism / Q000473:pathology
chemical_list: D018528:ATP-Binding Cassette Transporters; D007527:Isoenzymes; D053499:Plasma Membrane Calcium-Transporting ATPases; C506962:ATP2B3 protein, human; C403624:ATP2C1 protein, human; D000252:Calcium-Transporting ATPases; C548142:ATP11A protein, human
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