Journal article
Copy-number variants and candidate gene mutations in isolated split hand/foot malformation
Journal of human genetics, Vol.62(10), pp.877-884
10/2017
DOI: 10.1038/jhg.2017.56
PMCID: PMC5612852
PMID: 28539665
Abstract
Split hand/foot malformation (SHFM) is a congenital limb deficiency with missing or shortened central digits. Some SHFM genes have been identified but the cause of many SHFM cases is unknown. We used single nucleotide polymorphism (SNP) microarray analysis to detect copy-number variants (CNVs) in 25 SHFM cases without other birth defects from New York State (NYS), prioritized CNVs absent from population CNV databases, and validated these CNVs using qPCR. We tested for the validated CNVs in seven cases from Iowa using qPCR, and also sequenced 36 SHFM candidate genes in all subjects. Seven NYS cases had a potentially deleterious variant: two had a p.R225H or p.R225L mutation in
TP63
, one had a 17q25 microdeletion, one had a 10q24 microduplication, and three had a 17p13.3 microduplication. Additionally, one Iowa case had a
de novo
10q24 microduplication. The 17q25 microdeletion has not been reported previously in SHFM and included two SHFM candidate genes (
SUMO2
and
GRB2
), while the 10q24 and 17p13.3 CNVs had breakpoints within genomic regions that contained putative regulatory elements and a limb development gene. In SHFM pathogenesis, the microdeletion may cause haploinsufficiency of SHFM genes and/or deletion of their regulatory regions, and the microduplications could disrupt regulatory elements that control transcription of limb development genes.
Details
- Title: Subtitle
- Copy-number variants and candidate gene mutations in isolated split hand/foot malformation
- Creators
- Tonia C Carter - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, 50 South Drive, MSC 8004, Bethesda, MD 20892, USARobert J Sicko - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, 50 South Drive, MSC 8004, Bethesda, MD 20892, USADenise M Kay - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, 50 South Drive, MSC 8004, Bethesda, MD 20892, USAMarilyn L Browne - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, 50 South Drive, MSC 8004, Bethesda, MD 20892, USAPaul A Romitti - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, 50 South Drive, MSC 8004, Bethesda, MD 20892, USAZoë L Edmunds - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, 50 South Drive, MSC 8004, Bethesda, MD 20892, USAAiyi Liu - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, 50 South Drive, MSC 8004, Bethesda, MD 20892, USARuzong Fan - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, 50 South Drive, MSC 8004, Bethesda, MD 20892, USACharlotte M Druschel - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, 50 South Drive, MSC 8004, Bethesda, MD 20892, USAMichele Caggana - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, 50 South Drive, MSC 8004, Bethesda, MD 20892, USALawrence C Brody - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, 50 South Drive, MSC 8004, Bethesda, MD 20892, USAJames L Mills - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Building 50, 50 South Drive, MSC 8004, Bethesda, MD 20892, USA
- Resource Type
- Journal article
- Publication Details
- Journal of human genetics, Vol.62(10), pp.877-884
- DOI
- 10.1038/jhg.2017.56
- PMID
- 28539665
- PMCID
- PMC5612852
- NLM abbreviation
- J Hum Genet
- ISSN
- 1434-5161
- eISSN
- 1435-232X
- Publisher
- Springer Science and Business Media LLC
- Language
- English
- Date published
- 10/2017
- Academic Unit
- Epidemiology; Biostatistics
- Record Identifier
- 9983995001702771
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