title: A Novel IVS2-1G>A mutation causes aberrant splicing of the HRPT2 gene in a family with hyperparathyroidism-jaw tumor syndrome.
abstract: HRPT2, the gene associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome, was previously mapped to 1q24-q32. It was recently cloned, and several germline mutations were found to predispose to HPT-JT syndrome. We sequenced the complete HRPT2 coding sequence and splice-junctional regions in a Korean family with HPT-JT syndrome and identified a novel germline mutation, IVS2-1G>A in intron 2, that caused the autosomal dominant trait of HPT-JT syndrome in this family. RT-PCR and sequencing of the transcripts revealed that this splicing mutation generated alternative splicing errors leading to the formation of two different transcripts, one with exon 3 deleted, the other lacking the first 23 bp of exon 3 due to the use of an internal splice acceptor in exon 3. Translation of both transcripts results in premature termination. In addition, we detected two novel somatic mutations of HRPT2 in malignant parathyroid tumors from the affected individuals. One, 85delG, causes premature termination; the other, an 18 bp in-frame deletion of 13_30delCTTAGCGTCCTGCGACAG, suggests that this region may be important in the development of the parathyroid carcinomas in HPT-JT syndrome. These findings provide further evidence that mutation of HRPT2 is associated with the formation of parathyroid tumors in HPT-JT syndrome.
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul 137-701, Korea.
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Moon
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Eun-Min
authors.initials: EM
authors.lastname: Kim
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Je-Ho
authors.initials: JH
authors.lastname: Han
authors.forename: Soon-Jib
authors.initials: SJ
authors.lastname: Yoo
authors.forename: Kun-Ho
authors.initials: KH
authors.lastname: Yoon
authors.forename: Moo-Il
authors.initials: MI
authors.lastname: Kang
authors.forename: Kwang-Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Ho-Yong
authors.initials: HY
authors.lastname: Son
authors.forename: Sung-Koo
authors.initials: SK
authors.lastname: Kang
authors.forename: Se-Jeong
authors.initials: SJ
authors.lastname: Oh
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Kim
authors.forename: Sung-Joo Kim
authors.initials: SJ
authors.lastname: Yoon
authors.forename: Jae-Gahb
authors.initials: JG
authors.lastname: Park
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
authors.forename: Hio Chung
authors.initials: HC
authors.lastname: Kang
authors.forename: Soon-Won
authors.initials: SW
authors.lastname: Hong
authors.forename: Kyung-Rae
authors.initials: KR
authors.lastname: Kim
authors.forename: Bong-Yun
authors.initials: BY
authors.lastname: Cha
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D001483:Base Sequence; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D017931:DNA Primers; D005220:Fathers; D018095:Germ-Line Mutation; D006801:Humans; D006961:Hyperparathyroidism / Q000000981:diagnostic imaging / Q000235:genetics*; D007573:Jaw Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011859:Radiography; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013577:Syndrome; D025521:Tumor Suppressor Proteins
chemical_list: C454900:CDC73 protein, human; D017931:DNA Primers; D011506:Proteins; D025521:Tumor Suppressor Proteins