title: Genomic diagnosis by whole genome sequencing in a Korean family with atypical progeroid syndrome.
abstract: Clinical genomic diagnosis is unfamiliar to many dermatologists. Limited knowledge of bioinformatics has limited the use of the next generation sequencing method in dermatological clinics. We evaluated the usefulness of whole genome sequencing as a diagnostic approach to inherited dermatological disease. Here, we present our experience with two female siblings with atypical familial generalized lipodystrophy with diabetes mellitus and dyslipidemia. Whole genome sequencing was performed to diagnose the inherited disease. We compared control genomic databases using the Exome Aggregation Consortium, and filtered false-positive calls with the segmental duplication, non-flagged single nucleotide variants and COSMIC mutation databases, and applied the prediction tools of SIFT and PolyPhen2. The two siblings who presented with generalized lipodystrophy were diagnosed with an atypical progeroid syndrome with a p.D136H mutation in the LMNA gene (NM_005572). We diagnosed a familial atypical progeroid syndrome using whole genome sequencing. In this paper, we present our experience with whole genome sequencing and demonstrate that it can provide useful information for clinical genomic diagnosis of inherited diseases with atypical clinical features, such as atypical progeroid syndrome.
authors.affiliation: Seoul National University Hospital, Seoul, Korea.
authors.forename: Seungbok
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sae Mi
authors.initials: SM
authors.lastname: Park
authors.affiliation: Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jin-Wou
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Yu
authors.affiliation: Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Young Bok
authors.initials: YB
authors.lastname: Lee
mesh_terms: D000328:Adult; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation; D011371:Progeria / Q000175:diagnosis / Q000235:genetics*; D056910:Republic of Korea; D017422:Sequence Analysis, DNA; D035781:Siblings
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A
keywords: LMNA mutation; atypical progeroid syndrome; genomic diagnosis; next generation sequencing; whole genome sequencing