RT Journal Article
SR Electronic
T1 Whole genome analysis of an extended pedigree with Prader–Willi Syndrome, hereditary hemochromatosis, and dysautonomia-like symptoms
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 019182
DO 10.1101/019182
A1 Han Fang
A1 Yiyang Wu
A1 Margaret Yoon
A1 Laura T. Jiménez-Barrón
A1 Jason A. O’Rawe
A1 Gareth Highnam
A1 David Mittelman
A1 Gholson J. Lyon
YR 2015
UL http://biorxiv.org/content/early/2015/05/11/019182.abstract
AB This report includes the discovery and analysis of a pedigree with Prader–Willi Syndrome (PWS), hereditary hemochromatosis (HH), and dysautonomia-like symptoms. Nine members of the family participated in whole genome sequencing (WGS), which enabled a wide scope of variant calling from single-nucleotide polymorphisms to copy number variations. First, a 5.5 Mb de novo deletion is identified in the chromosome region 15q11.2 to 15q13.1 in the boy with PWS. Second, a female invididual with HH is homozygous for the p.C282Y variant in HFE, a mutation known to be associated with HH. Her brother is homozygous for the same variant, although he has yet to be clinically diagnosed with HH. Third, none of the people with dysautonomia-like symptoms carry any reported or novel rare variants in IKBKAP that are implicated in familial dysautonomia (FD - HSAN III). Although two people with dysautonomia-like symptoms carry two heterozygous variants in NTRK1, a gene that has been shown to contribute to HSAN IV (congenital insensitivity to pain with anhidrosis, a disease that closely resembles FD), this variant is not present in the third proband. Fourth, WGS revealed pharmacogenetic variants influencing the metabolism of warfarin and simvastatin, which are being routinely prescribed to the proband. Finally, reports of the phenotypes were standardized with the Human Phenotype Ontology annotation, which may facilitate the search for other families with similar phenotypes. Due to the extreme heterogeneity and insufficient knowledge of human diseases, it is of crucial importance that both phenotypic data and genomic data are standardized and shared.(SNP)Single-nucleotide polymorphism(CNV)copy number variantion(INDELs)insertions and deletions(SV)structual variant(WGS)whole genome sequencing(WES)whole exome sequencing(NGS)next-generation sequencing(base pair)bp(kilo base pairs)Kb(megabase pair)Mb(polymerase chain reaction)PCR(PWS)Prader–Willi syndrome(HH)hereditary hemochromatosis(FD)familial dysautonomia(CIPA)congenital insensitivity to pain with anhidrosis(TS)Tourette syndrome(HPO)the Human Phenotype Ontology(OCD)obsessive-compulsive disorder