HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours.

Abstract:

BACKGROUND:Hyperparathyroidism is a common endocrinopathy characterised by the formation of parathyroid tumours. In this study, we determine the role of the recently identified gene, HRPT2, in parathyroid tumorigenesis. METHODS:Mutation analysis of HRPT2 was undertaken in 60 parathyroid tumours: five HPT-JT, three FIHP, three MEN 1, one MEN 2A, 25 sporadic adenomas, 17 hyperplastic glands, two lithium associated tumours, and four sporadic carcinomas. Loss of heterozygosity at 1q24-32 was performed on a subset of these tumours. RESULTS:HRPT2 somatic mutations were detected in four of four sporadic parathyroid carcinoma samples, and germline mutations were found in five of five HPT-JT parathyroid tumours (two families) and two parathyroid tumours from one FIHP family. One HPT-JT tumour with germline mutation also harboured a somatic mutation. In total, seven novel and one previously reported mutation were identified. "Two-hits" (double mutations or one mutation and loss of heterozygosity at 1q24-32) affecting HRPT2 were found in two sporadic carcinomas, two HPT-JT-related and two FIHP related tumours. CONCLUSIONS:The results in this study support the role of HRPT2 as a tumour suppressor gene in sporadic parathyroid carcinoma, and provide further evidence for HRPT2 as the causative gene in HPT-JT, and a subset of FIHP. In light of the strong association between mutations of HRPT2 and sporadic parathyroid carcinoma demonstrated in this study, it is hypothesised that HRPT2 mutation is an early event that may lead to parathyroid malignancy and suggest intragenic mutation of HRPT2 as a marker of malignant potential in both familial and sporadic parathyroid tumours.

journal_name

J Med Genet

authors

Howell VM,Haven CJ,Kahnoski K,Khoo SK,Petillo D,Chen J,Fleuren GJ,Robinson BG,Delbridge LW,Philips J,Nelson AE,Krause U,Hammje K,Dralle H,Hoang-Vu C,Gimm O,Marsh DJ,Morreau H,Teh BT

doi

10.1136/jmg.40.9.657

keywords:

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

657-63

issue

9

eissn

0022-2593

issn

1468-6244

journal_volume

40

pub_type

杂志文章
  • Echinocytes in families with Duchenne muscular dystrophy.

    abstract::The results of the present investigation have failed to confirm the suggestion that there is a significant increase in the proportion of echinocytes in preparation of fresh erythrocytes in patients with Duchenne muscular dystrophy and heterozygous carriers of this disorder. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.14.4.276

    authors: Soltan HC

    更新日期:1977-08-01 00:00:00

  • Interstitial deletion in the long arms of chromosome 1: 46,XY,del(1)(pter leads to q22::q25 leads to qter).

    abstract::A child was brought to us with multiple anomalies. On examination we found an interstitial deletion in the long arms of chromosome 1. We studied genetic and chromosome markers, comparing our clinical and cytogenetic findings with other reported cases of chromosome 1 interstitial deletion. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.17.6.483

    authors: de Pablo CE,García Sagredo JM,Ferro MT,Ferrando P,San Román C

    更新日期:1980-12-01 00:00:00

  • Normal and aberrant splicing of LMNA.

    abstract::The LMNA gene gives rise to at least three isoforms (lamin A, C, lamin AΔ10) as a result of normal alternative splicing, regulated by cis- and trans-acting regulatory factors, as well as the 5' and 3' untranslated regions of the gene. The two main isoforms, lamin A and C, are constitutive components of the fibrous nuc...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,评审

    doi:10.1136/jmedgenet-2013-102119

    authors: Luo YB,Mastaglia FL,Wilton SD

    更新日期:2014-04-01 00:00:00

  • Studies of genetic linkage between adult polycystic kidney disease and three markers on chromosome 16.

    abstract::Adult polycystic kidney disease (APKD) is a common genetic disorder that is inherited as an autosomal dominant trait. Recent reports show that, in some families, the APKD gene shows close genetic linkage to two chromosome 16 specific genetic markers. We have been conducting a genetic linkage study using 29 polymorphic...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.24.8.457

    authors: Watson ML,Wright AF,Macnicol AM,Allan PL,Clayton JF,Dempster M,Jeremiah SJ,Corney G,Hopkinson DA

    更新日期:1987-08-01 00:00:00

  • Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries.

    abstract::Approximately 5%-10% of breast cancers are due to genetic predisposition caused by germline mutations; the most commonly tested genes are BRCA1 and BRCA2 mutations. Some mutations are unique to one family and others are recurrent; the spectrum of BRCA1/BRCA2 mutations varies depending on the geographical origins, popu...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,评审

    doi:10.1136/jmedgenet-2015-103132

    authors: Kwong A,Shin VY,Ho JC,Kang E,Nakamura S,Teo SH,Lee AS,Sng JH,Ginsburg OM,Kurian AW,Weitzel JN,Siu MT,Law FB,Chan TL,Narod SA,Ford JM,Ma ES,Kim SW

    更新日期:2016-01-01 00:00:00

  • Immunogenetic factors in aetiology of pre-eclampsia/eclampsia (gestosis).

    abstract::The evidence that genetic and immunogenetic influences operate in the causation of pre-eclampsia/eclampsia (gestosis) is reviewed. The problems of definitive diagnosis are discussed along with the possibility of a multifactorial aetiology. The difficulties of differentiating trigger and effector mechanisms are also co...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.13.3.200

    authors: Scott JS,Jenkins DM

    更新日期:1976-06-01 00:00:00

  • Trisomy 18 syndrome with an unusual karyotype: possible double isochromosome.

    abstract::Chromosome analysis of an infant with characteristic features of trisomy 18 is presented. The chromosome complement contained a modal count of 47 but there was only one No. 18. In addition, there were two metacentric chromosomes of different sizes. The two metacentric chromosomes were identified by G- and C-banding to...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.15.1.73

    authors: Larson LM,Wasdahl WA,Saumur JH,Coleman ML,Jalal SM

    更新日期:1978-02-01 00:00:00

  • Factors determining penetrance in familial atypical haemolytic uraemic syndrome.

    abstract:BACKGROUND:Inherited abnormalities of complement are found in ∼60% of patients with atypical haemolytic uraemic syndrome (aHUS). Such abnormalities are not fully penetrant. In this study, we have estimated the penetrance of the disease in three families with a CFH mutation (c.3643C>G; p. Arg1215Gly) in whom a common li...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmedgenet-2014-102498

    authors: Sansbury FH,Cordell HJ,Bingham C,Bromilow G,Nicholls A,Powell R,Shields B,Smyth L,Warwicker P,Strain L,Wilson V,Goodship JA,Goodship TH,Turnpenny PD

    更新日期:2014-11-01 00:00:00

  • Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome.

    abstract:BACKGROUND:Biallelic germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 or PMS2 cause a recessive childhood cancer syndrome characterised by early-onset malignancies and signs reminiscent of neurofibromatosis type 1 (NF1). Alluding to the underlying genetic defect, we refer to this syndrome as constitutio...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.2008.064212

    authors: Kratz CP,Holter S,Etzler J,Lauten M,Pollett A,Niemeyer CM,Gallinger S,Wimmer K

    更新日期:2009-06-01 00:00:00

  • Familial adenomatous polyposis associated with multiple adrenal adenomas in a patient with a rare 3' APC mutation.

    abstract::Familial adenomatous polyposis (FAP) is characterised by hundreds of colorectal adenomas. Endocrine neoplasms have occasionally been reported, as have gastric polyps, which are usually hamartomatous in the fundus of the stomach and adenomatous in the antrum. A 57 year old man with colorectal, gastric, and periampullar...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:

    authors: Kartheuser A,Walon C,West S,Breukel C,Detry R,Gribomont AC,Hamzehloei T,Hoang P,Maiter D,Pringot J,Rahier J,Khan PM,Curtis A,Burn J,Fodde R,Verellen-Dumoulin C

    更新日期:1999-01-01 00:00:00

  • "Compensatory" uniparental disomy of chromosome 21 in two cases.

    abstract::Two cases of growth failure, microcephaly, facial dysmorphism, muscular hypertonia, and severe psychomotor retardation are described. At birth, both cases had cytogenetic mosaicism in lymphocytes and skin fibroblasts, in case 1 ring chromosome 21 and monosomy 21 and in case 2, deletion of chromosome 21 and monosomy 21...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.31.7.534

    authors: Bartsch O,Petersen MB,Stuhlmann I,Mau G,Frantzen M,Schwinger E,Antonarakis SE,Mikkelsen M

    更新日期:1994-07-01 00:00:00

  • A pedigree analysis with minimised ascertainment bias shows anticipation in Met30-transthyretin related familial amyloid polyneuropathy.

    abstract::In type I familial amyloid polyneuropathy (FAP) caused by a variant Met30-transthyretin (TTR), genetic anticipation has been reported. To determine whether anticipation of the disease is a true biological phenomenon or the result of ascertainment bias, we compared age at onset of the affected child with that of the af...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.35.1.23

    authors: Yamamoto K,Ikeda S,Hanyu N,Takeda S,Yanagisawa N

    更新日期:1998-01-01 00:00:00

  • Homozygous missense mutation in MED25 segregates with syndromic intellectual disability in a large consanguineous family.

    abstract:BACKGROUND:Intellectual disability (ID) is a highly heterogeneous condition affecting 2% of the population worldwide. In a field study conducted in a highly inbred area of Northeastern Brazil, we investigated a consanguineous family in which seven adults presented syndromic ID. METHODS:Genome-Wide Human SNP Array 6.0 ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmedgenet-2014-102793

    authors: Figueiredo T,Melo US,Pessoa AL,Nobrega PR,Kitajima JP,Correa I,Zatz M,Kok F,Santos S

    更新日期:2015-02-01 00:00:00

  • Cyclophosphamide increases the frequency of sister chromatid exchange in direct preparations of human chorionic villi in the absence of supplementary enzymatic activation systems.

    abstract::A study was performed to evaluate the effect on the frequency of sister chromatid exchange in first trimester chorionic villi of two chemical compounds, mitomycin C and cyclophosphamide. Mitomycin C is generally known to induce an increase in sister chromatid exchange both in vivo and in vitro standard conditions. Cyc...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.29.2.109

    authors: Pariani S,Buscaglia M,Piantanida M,Simoni G

    更新日期:1992-02-01 00:00:00

  • Chromosome survey of total population of mentally subnormal in North-East of Scotland.

    abstract::A cytogenetic survey of the complete population of mentally subnormal in the North-East of Scotland has been undertaken. A register for the mentally subnormal within the region already existed, and all persons recorded, whether they resided at home or in subnormality hospitals or other institutional care, were include...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.13.4.295

    authors: Speed RM,Johnston AW,Evans HJ

    更新日期:1976-08-01 00:00:00

  • Analysis of a terminal Xp22.3 deletion in a patient with six monogenic disorders: implications for the mapping of X linked ocular albinism.

    abstract::The molecular characterisation of chromosomal aberrations in Xp22.3 has established the map position of several genes with mutations resulting in diverse phenotypes such as short stature (SS), chondrodysplasia punctata (CDPX), mental retardation (MRX), ichthyosis (XLI), and Kallmann syndrome (KAL). We describe the cli...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.30.10.838

    authors: Meindl A,Hosenfeld D,Brückl W,Schuffenhauer S,Jenderny J,Bacskulin A,Oppermann HC,Swensson O,Bouloux P,Meitinger T

    更新日期:1993-10-01 00:00:00

  • Choanal atresia as a feature of ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome.

    abstract::We report here a father and daughter with digital abnormalities, nasolacrimal duct obstruction, and variable alopecia. The father had a cleft lip and palate and the daughter had choanal atresia. We propose they both have the EEC syndrome and show the variable expressivity of this disorder. Choanal atresia has not been...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.26.9.586

    authors: Christodoulou J,McDougall PN,Sheffield LJ

    更新日期:1989-09-01 00:00:00

  • Anal atresia and the Klein-Waardenburg syndrome.

    abstract::A 3-month-old male infant with type I Klein-Waardenburg syndrome with an imperforated anus and a perineal fistula is reported. The possible association of this gastrointestinal malformation with the KW syndrome is discussed. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.18.3.239

    authors: Nutman J,Nissenkorn I,Varsano I,Mimouni M,Goodman RM

    更新日期:1981-06-01 00:00:00

  • Haematological and obstetric aspects of antenatal diagnosis of beta-thalassaemia: experience with 200 cases.

    abstract::The results of 200 antenatal diagnoses in pregnancies at risk for homozygous beta-thalassaemia, carried out on fetal blood samples obtained by placental aspiration in the second trimester, are described. Globin chain synthesis in the fetuses was measured by means of 3H-leucine incorporation and separation of the chain...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.19.2.81

    authors: Cao A,Furbetta M,Angius A,Ximenes A,Rosatelli C,Tuveri T,Scalas MT,Falchi AM,Angioni G,Caminiti F

    更新日期:1982-04-01 00:00:00

  • Identification of novel MUNC13-4 mutations in familial haemophagocytic lymphohistiocytosis and functional analysis of MUNC13-4-deficient cytotoxic T lymphocytes.

    abstract:BACKGROUND:Familial haemophagocytic lymphohistiocytosis (FHL) has an autosomal recessive mode of inheritance and consists of at least three subtypes. FHL2 subtype with perforin (PRF1) mutation accounts for 30% of all FHL cases, while FHL with MUNC13-4 mutation was recently identified and designated as FHL3 subtype. OB...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.2004.021121

    authors: Yamamoto K,Ishii E,Sako M,Ohga S,Furuno K,Suzuki N,Ueda I,Imayoshi M,Yamamoto S,Morimoto A,Takada H,Hara T,Imashuku S,Sasazuki T,Yasukawa M

    更新日期:2004-10-01 00:00:00

  • Association of the 103I MC4R allele with decreased body mass in 7937 participants of two population based surveys.

    abstract:BACKGROUND:The melanocortin-4-receptor gene (MC4R) is part of the melanocortinergic pathway that controls energy homeostasis. In a recent meta-analysis, the MC4R V103I (rs2229616) polymorphism was shown to be associated with body weight regulation. Although no functional differences between the isoleucine comprising re...

    journal_title:Journal of medical genetics

    pub_type: 信件

    doi:10.1136/jmg.2004.027011

    authors: Heid IM,Vollmert C,Hinney A,Döring A,Geller F,Löwel H,Wichmann HE,Illig T,Hebebrand J,Kronenberg F,KORA Group.

    更新日期:2005-04-01 00:00:00

  • Prenatal diagnosis of the common haemoglobin disorders.

    abstract::New techniques of DNA analysis have been applied to the prenatal diagnosis of the common haemoglobin disorders. Currently, it is possible to provide a comprehensive programme for the prevention of these conditions, although this entails the use of several different techniques including globin chain synthesis analysis,...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,评审

    doi:10.1136/jmg.22.6.422

    authors: Weatherall DJ,Old JM,Thein SL,Wainscoat JS,Clegg JB

    更新日期:1985-12-01 00:00:00

  • High frequency of submicroscopic chromosomal imbalances in patients with syndromic craniosynostosis detected by a combined approach of microsatellite segregation analysis, multiplex ligation-dependent probe amplification and array-based comparative genome

    abstract::We present the first comprehensive study, to our knowledge, on genomic chromosomal analysis in syndromic craniosynostosis. In total, 45 patients with craniosynostotic disorders were screened with a variety of methods including conventional karyotype, microsatellite segregation analysis, subtelomeric multiplex ligation...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.2007.057042

    authors: Jehee FS,Krepischi-Santos AC,Rocha KM,Cavalcanti DP,Kim CA,Bertola DR,Alonso LG,D'Angelo CS,Mazzeu JF,Froyen G,Lugtenberg D,Vianna-Morgante AM,Rosenberg C,Passos-Bueno MR

    更新日期:2008-07-01 00:00:00

  • Ocular colobomata, cardiac defect, and other anomalies: a study of seven cases including two sibs.

    abstract::An association of ocular colobomata and congenital heart disease was observed in seven patients. Two of these were maternal half sisters whose mother also had ocular colobomata. All the patients had normal karyotypes. There was a high incidence of other associated abnormalities involving the central nervous, skeletal,...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.12.3.289

    authors: Ho CK,Kaufman RL,Podos SM

    更新日期:1975-09-01 00:00:00

  • Maternal uniparental disomy for chromosome 14 in a boy with a normal karyotype.

    abstract::We report on a boy with a maternal uniparental disomy for chromosome 14 (UPD(14)). At 7 years of age he was referred to us by the paediatrician because of symptoms of Prader-Willi syndrome (PWS). He showed short stature, obesity, mild developmental delay, cryptorchidism, and some mild dysmorphic features. The history ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章,评审

    doi:10.1136/jmg.36.10.782

    authors: Hordijk R,Wierenga H,Scheffer H,Leegte B,Hofstra RM,Stolte-Dijkstra I

    更新日期:1999-10-01 00:00:00

  • A combination of genetic polymorphisms increases the risk of progressive disease in chronic hepatitis C.

    abstract:BACKGROUND:There is increasing interest in the influence of host genetic factors on hepatic fibrosis, and whether genetic markers can reliably identify subjects at risk of developing severe disease. We hypothesised that hepatitis C virus (HCV) infected subjects with progressive fibrosis, classified using strict criteri...

    journal_title:Journal of medical genetics

    pub_type: 信件

    doi:10.1136/jmg.2005.032557

    authors: Richardson MM,Powell EE,Barrie HD,Clouston AD,Purdie DM,Jonsson JR

    更新日期:2005-07-01 00:00:00

  • Epigenetic state and expression of imprinted genes in umbilical cord correlates with growth parameters in human pregnancy.

    abstract:BACKGROUND:Genomic imprinting is a process causing genes to be expressed according to parental origin. Imprinting acts to coordinate fetal and prenatal growth, as well as control postnatal adaptations. Studies on human imprinting are confounded by tissue availability, sampling variability and limitations posed by tissu...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmedgenet-2012-100858

    authors: Lim AL,Ng S,Leow SC,Choo R,Ito M,Chan YH,Goh SK,Tng E,Kwek K,Chong YS,Gluckman PD,Ferguson-Smith AC

    更新日期:2012-11-01 00:00:00

  • Apolipoprotein CII-Padova (Tyr37-->stop) as a cause of chylomicronaemia in an Italian kindred from Siculiana.

    abstract::In this paper we report on the molecular defect underlying apolipoprotein CII (apoCII) deficiency in an Italian kindred. ApoCII serves as cofactor for lipoprotein lipase (LPL) in triglyceride hydrolysis of chylomicrons and very low density lipoproteins. Homozygous apoCII deficiency manifests with type I hyperlipoprote...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.31.8.622

    authors: Tuzgöl S,Bijvoet SM,Bruin T,Kastelein JJ,Hayden MR

    更新日期:1994-08-01 00:00:00

  • Porencephalic cyst in pycnodysostosis.

    abstract::We describe a case of pycnodysostosis with porencephaly and suggest an explanation for the porencephaly by a mechanism of imbalance between brain growth and its vascular supply and a normal but unopposed cerebrospinal fluid pressure. ...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.26.12.782

    authors: Figueiredo J,Reis A,Vaz R,Leáo M,Cruz C

    更新日期:1989-12-01 00:00:00

  • Congenital heart disease is a feature of severe infantile spinal muscular atrophy.

    abstract:OBJECTIVE:Homozygous deletions/mutations of the SMN1 gene cause infantile spinal muscular atrophy (SMA). The presence of at least one SMN2 gene copy is required for normal embryogenesis. Lack of SMN protein results in degeneration of motor neurons, while extraneuronal manifestations have been regarded as a chance assoc...

    journal_title:Journal of medical genetics

    pub_type: 杂志文章

    doi:10.1136/jmg.2008.057950

    authors: Rudnik-Schöneborn S,Heller R,Berg C,Betzler C,Grimm T,Eggermann T,Eggermann K,Wirth R,Wirth B,Zerres K

    更新日期:2008-10-01 00:00:00