Publication:
DNAJC3 mutation in Thai familial type 2 diabetes mellitus

dc.contributor.authorSirikul Kulanuwaten_US
dc.contributor.authorWatip Tangjittipokinen_US
dc.contributor.authorPrapaporn Jungtrakoonen_US
dc.contributor.authorChutima Chanpraserten_US
dc.contributor.authorJatuporn Sujjitjoonen_US
dc.contributor.authorNinareeman Binnimaen_US
dc.contributor.authorPa Thai Yenchitsomanusen_US
dc.contributor.authorNattachet Plengvidhyaen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherFaculty of Medicine, Siriraj Hospital, Mahidol Universityen_US
dc.date.accessioned2019-08-23T10:38:51Z
dc.date.available2019-08-23T10:38:51Z
dc.date.issued2018-01-01en_US
dc.description.abstract© 2018 Spandidos Publications. All rights reserved. Type 2 diabetes mellitus (T2D) is a heterogeneous disease, with certain cases presenting an autosomal dominant type. The rare coding variants of disease-causing genes in T2D remain mostly unclear. The present study aimed to identify the disease-causing gene conducting whole exome sequencing in a Thai T2D family with an autosomal dominant transmission of T2D with no evidence of mutations in known maturity-onset diabetes of the young (MODY) genes. Candidate variants were selected according to certain criteria of mutation prediction programs, followed by segregation analysis with diabetes in the family. The results demonstrated that, of the 68,817 variants obtained, 122 were considered as candidate variants subsequent to the filtering processes. Genotyping of these variants revealed that DnaJ homolog subfamily C member 3 (DNAJC3) p.H238N segregated with diabetes in the family. This mutation was also identified in another proband from the autosomal dominant T2D family without mutation in known MODY genes and was segregated with diabetes. This variant was also identified in 14/1,000 older-onset T2D patients [minor allele frequency (MAF)=0.007], 2/500 non-diabetic controls (MAF=0.002) and 3 prediabetic individuals who were previously classified as non-diabetic controls. In silico mutagenesis and protein modeling of p.H238N revealed changes of the polar contacts across the tetratricopeptide repeat (TPR) motif and TPR subdomains, which may affect the protein tertiary structure. Furthermore, the expression of DNAJC3 H238N protein was 0.68±0.08 fold (P<0.05) lower when compared with that of the wild-type, possibly due to protein instability. Thus, DNAJC3 p.H238N is likely to be a variant causing diabetes.en_US
dc.identifier.citationInternational Journal of Molecular Medicine. Vol.42, No.2 (2018), 1064-1073en_US
dc.identifier.doi10.3892/ijmm.2018.3678en_US
dc.identifier.issn1791244Xen_US
dc.identifier.issn11073756en_US
dc.identifier.other2-s2.0-85054777955en_US
dc.identifier.urihttps://repository.li.mahidol.ac.th/handle/20.500.14594/45281
dc.rightsMahidol Universityen_US
dc.rights.holderSCOPUSen_US
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85054777955&origin=inwarden_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titleDNAJC3 mutation in Thai familial type 2 diabetes mellitusen_US
dc.typeArticleen_US
dspace.entity.typePublication
mu.datasource.scopushttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85054777955&origin=inwarden_US

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