title: Genome-wide linkage analysis and whole-genome sequencing identify a recurrent SMARCAD1 variant in a unique Chinese family with Basan syndrome.
abstract: Basan syndrome is a rare autosomal dominant genodermatosis, characterized by rapidly healing congenital acral bullae, congenital milia and lack of fingerprints. A mutation in the SMARCAD1 gene was recently reported to cause Basan syndrome in one family. Here, we present a large Chinese family with Basan syndrome; some patients presented with hyperpigmentation and knuckle pads in addition to previously reported clinical manifestations. We used genome-wide linkage analysis and whole-genome sequencing (WGS) to identify the pathogenic gene in this unique pedigree. Genome-wide linkage analysis successfully mapped the candidate gene to 4p15.31-4p14 and 4q13.2-4q23. The maximal LOD score was 3.01. WGS in one patient identified a splice variant (c.378+1G>T) in the SMARCAD1 gene (NG_031945.1) that was confirmed by Sanger sequencing. Co-segregation of the variant was confirmed in this pedigree. The same variant was recently found to be associated with isolated adermatoglyphia (ADG) in another family, suggesting that this variant is causative for both Basan syndrome and autosomal dominant ADG (OMIM 136 000). This indicates that ADG and Basan syndrome may be the phenotypic variants of the same disease. Further studies should be performed to elucidate the pathogenic mechanisms induced by this variant. This report increases the phenotypic spectrum of Basan syndrome and furthers our understanding of the genetic basis of this disease. Our results also highlight the power of combining WGS and genome-wide linkage analysis in identifying causative genes in pedigrees with a genetic disorder.
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
authors.forename: Zhenlu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ni
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ruhong
authors.initials: R
authors.lastname: Cheng
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000328:Adult; D002648:Child; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004476:Ectodermal Dysplasia / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009154:Mutation; D009264:Nails, Malformed / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012326:RNA Splicing
chemical_list: C561641:SMARCAD1 protein, human; D004265:DNA Helicases