Parafibromin mutations in hereditary hyperparathyroidism syndromes and parathyroid tumours.


OBJECTIVE:To investigate two patients with the hyperparathyroidism-jaw tumour (HPT-JT) syndrome and three patients with familial isolated hyperparathyroidism (FIHP), together with 31 parathyroid tumours (2 HPT-JT, 2 FIHP and 27 sporadic) for HRPT2 mutations. The HPT-JT syndrome and FIHP are autosomal dominant disorders that may be caused by abnormalities of the HRPT2 gene, located on chromosome 1q31.2. HRPT2 encodes a 531 amino acid protein, parafibromin, which interacts with human homologues of the yeast Paf1 complex. DESIGN:Leukocyte and tumor DNA was used with HRPT2-specific primers for polymerase chain reaction amplification of the 17 exons and their splice junctions, and the DNA sequences of the polymerase chain reaction products determined. RESULTS:Three heterozygous germline HRPT2 mutations, two in HPT-JT and one in FIHP patients, were identified. These consisted of one 1-bp duplication (745dup1bp), 1 nonsense (Arg234Stop) and 1 missense (Asp379Asn) mutation. One parathyroid tumour from an FIHP patient was demonstrated to harbour a germline deletion of 1 bp together with a somatic missense (Leu95Pro) mutation, consistent with a 'two-hit' model for hereditary cancer. The 27 sporadic benign parathyroid tumours did not harbour any HRPT2 somatic mutations. Six HRPT2 polymorphisms with allele frequencies ranging from 2% to 15% were detected. CONCLUSIONS:Our results have identified three novel HRPT2 mutations (two germline and one somatic). The Asp379Asn mutation is likely to disrupt interaction with the human homologue of the yeast Paf1 complex, and the demonstration of combined germline and somatic HRPT2 mutations in a parathyroid tumour provide further evidence for the tumour suppressor role of the HRPT2 gene.


Clin Endocrinol (Oxf)


Clinical endocrinology


Bradley KJ,Cavaco BM,Bowl MR,Harding B,Cranston T,Fratter C,Besser GM,Conceição Pereira M,Davie MW,Dudley N,Leite V,Sadler GP,Seller A,Thakker RV





Has Abstract


2006-03-01 00:00:00














  • Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population.

    abstract:OBJECTIVE:Mutations in the melanocortin-4 receptor gene (MC4R) are the most common monogenic form of human obesity. However, the contribution of MC4R mutations to obesity in Chinese has not been investigated. We studied the frequency of MC4R mutations in an obese southern Chinese population and the functional consequen...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Rong R,Tao YX,Cheung BM,Xu A,Cheung GC,Lam KS

    更新日期:2006-08-01 00:00:00

  • Establishment and evaluation of a novel biomarker-based nomogram for malignant phaeochromocytomas and paragangliomas.

    abstract:OBJECTIVE:No single histological or molecular marker is diagnostic for malignant phaeochromocytomas and paragangliomas (PPGLs). This study aimed to establish and evaluate a prognostic nomogram to improve the prediction of metastatic probability in individual PPGL patients. METHODS:Three hundred and 47 consecutive PPGL...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Zhong X,Ye L,Su T,Xie J,Zhou W,Jiang Y,Jiang L,Ning G,Wang W

    更新日期:2017-08-01 00:00:00

  • Growth hormone (GH) secretion and response to GH therapy after total body irradiation and haematopoietic stem cell transplantation during childhood.

    abstract:OBJECTIVE:In January 1997 we introduced a protocol for the treatment with GH of children with impaired growth after unfractionated total body irradiation (TBI). This study is an evaluation of that protocol. PATIENTS AND METHODS:Between January 1997 and July 2005, 66 patients (48 male) treated for haematological malign...

    journal_title:Clinical endocrinology

    pub_type: 临床试验,杂志文章


    authors: Bakker B,Oostdijk W,Geskus RB,Stokvis-Brantsma WH,Vossen JM,Wit JM

    更新日期:2007-10-01 00:00:00

  • Individual neurophysin concentrations in the pituitary and circulation of humans.

    abstract::Specific, homologous human neurophysin I and II radioimmunoassays were established and used to measure the individual, immunoreactive neurophysin concentrations in human plasma. Circulating levels of human neurophysin I in normal individuals were less than 1 ng/ml and neurophysin II levels were 1-2 ng/ml. During dehyd...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Dax EM,Clappison BH,Pullan PT,Pepperell R,Johnston CI

    更新日期:1979-03-01 00:00:00

  • Growth hormone response to low dose intravenous injections of growth hormone releasing factor in obese and normal weight women.

    abstract::We have recently reported an impaired growth hormone (GH) response to a single i.v. bolus dose of growth hormone releasing factor (1 microgram/kg body weight) in obese women. We have now investigated whether the i.v. administration of low dose GHRF(1-29)NH2 (0.33 microgram/kg/h) by 15 min pulsed injections for 3 h fol...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Kopelman PG,Noonan K

    更新日期:1986-02-01 00:00:00

  • Extra-adrenal effects of metyrapone include inhibition of the 11-oxoreductase activity of 11 beta-hydroxysteroid dehydrogenase: a model for 11-HSD I deficiency.

    abstract:BACKGROUND AND OBJECTIVE:Previous studies suggesting effects of metyrapone on extra-adrenal corticosteroid metabolism have involved significant alterations in plasma cortisol. We have therefore studied effects of metyrapone on urinary excretion of steroids in a group of patients treated concurrently with hydrocortisone...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Raven PW,Checkley SA,Taylor NF

    更新日期:1995-11-01 00:00:00

  • Impaired circulating glucagon-like peptide-1 response to oral glucose in women with previous gestational diabetes.

    abstract:BACKGROUND AND OBJECTIVE:Women with previous gestational diabetes (pGDM) are at risk of developing Type 2 diabetes. Glucagon-like peptide-1 (GLP-1) potentiates the insulin response to oral glucose, and its secretion is diminished in Type 2 diabetes. The aim of the study was to see if decreased GLP-1 secretion might be ...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Forbes S,Moonan M,Robinson S,Anyaoku V,Patterson M,Murphy KG,Ghatei MA,Bloom SR,Johnston DG

    更新日期:2005-01-01 00:00:00

  • Transdermal oestradiol replacement therapy enhances platelet constitutive nitric oxide synthase activity in postmenopausal women with type 2 diabetes mellitus.

    abstract:OBJECTIVE:To determine whether treatment with transdermal oestrogen replacement therapy (TERT) in postmenopausal women with type 2 diabetes mellitus was able to increase the activity of constitutive nitric oxide synthase (cNOS) in platelets. RESEARCH DESIGN AND METHODS:Eighteen postmenopausal women with type 2 diabete...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Martina V,Bruno GA,Origlia C,Gaia D,Trucco F,Pescarmona G

    更新日期:2002-09-01 00:00:00

  • FHIT and TSG101 in thyroid tumours: aberrant transcripts reflect rare abnormal RNA processing events of uncertain pathogenetic or clinical significance.

    abstract:OBJECTIVE:The chromosomal regions containing the two putative tumour suppressors, fragile histidine triad gene (FHIT) and tumour suppressor gene 101 (TSG101), are deleted frequently in thyroid tumours. We therefore analysed FHIT and TSG101 transcripts in a group of advanced thyroid tumours to establish their role in th...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: McIver B,Grebe SK,Wang L,Hay ID,Yokomizo A,Liu W,Goellner JR,Grant CS,Smith DI,Eberhardt NL

    更新日期:2000-06-01 00:00:00

  • Central cervical lymph node metastases in papillary thyroid cancer: a systematic review of imaging-guided and prophylactic removal of the central compartment.

    abstract:BACKGROUND:Papillary thyroid cancer (PTC) is a common endocrine cancer and commonly presents with lymph node (LN) metastases. The role of surgical removal of the central cervical LN compartment is poorly defined. There are no prospective randomized controlled trials addressing the relevance to the extent of the initial...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章,meta分析,评审


    authors: Mulla M,Schulte KM

    更新日期:2012-01-01 00:00:00

  • The relationship between cortisol production rate and serial serum cortisol estimation in patients on medical therapy for Cushing's syndrome.

    abstract:OBJECTIVE:The aim was to determine the target range into which mean daily serum cortisol should be lowered in patients on medical therapy for Cushing's syndrome, using isotopically estimated cortisol production rates as 'gold standard'. DESIGN:Patients with Cushing's syndrome on medical treatment were given 12 ng of t...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Trainer PJ,Eastment C,Grossman AB,Wheeler MJ,Perry L,Besser GM

    更新日期:1993-10-01 00:00:00

  • Pulsed tissue Doppler identifies subclinical myocardial biventricular dysfunction in active acromegaly.

    abstract:OBJECTIVE:The aim of this study was to assess the role of pulsed tissue Doppler (TD) to identify left (LV) and right ventricular (RV) myocardial regional involvement in acromegaly. PATIENTS AND MEASUREMENTS:Thirty active acromegaly patients, free of diabetes mellitus, thyroid dysfunction, valvular and coronary heart d...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Galderisi M,Vitale G,Bianco A,Pivonello R,Lombardi G,Divitiis Od,Colao A

    更新日期:2006-04-01 00:00:00

  • The relationship between the growth hormone and insulin-like growth factor axis in long-term survivors of childhood brain tumours.

    abstract:OBJECTIVE:We compared IGF-1 and IGFBP3 concentrations in a group of adults treated for brain tumours in childhood with those of matched controls, and investigated the relationship between the GH secretory pattern and IGF-1/IGFBP3 concentrations in the entire group. DESIGN:We performed 24 h serum GH profiles using 20 m...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Achermann JC,Hindmarsh PC,Brook CG

    更新日期:1998-11-01 00:00:00

  • Normal VLDL metabolism despite altered lipoprotein composition in type 1 diabetes mellitus.

    abstract:OBJECTIVES:Patients with type 1 diabetes are at increased risk of cardiovascular disease, which may be related to abnormal lipid metabolism. Secretion and clearance of VLDL apolipoprotein B100 (apoB) are important determinants of plasma lipid concentrations and are known to be influenced by hormones, including insulin ...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Christ ER,Carroll PV,Albany E,Umpleby AM,Lumb PJ,Wierzbicki AS,Simpson HL,Sönksen PH,Russell-Ones DL

    更新日期:2001-12-01 00:00:00

  • The PPAR-gamma activator rosiglitazone fails to lower plasma ACTH levels in patients with Nelson's syndrome.

    abstract:BACKGROUND:Peroxisomal proliferator-activated receptors (PPAR)- gamma are expressed abundantly in ACTH-secreting pituitary tumours. The PPAR-gamma activator rosiglitazone has been shown to suppress ACTH secretion in human adrenocorticotroph tumour cells in vitro, and prevent and reduce adrenocorticotroph tumour develop...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Mullan KR,Leslie H,McCance DR,Sheridan B,Atkinson AB

    更新日期:2006-05-01 00:00:00

  • Radiation and neuroregulatory control of growth hormone secretion.

    abstract:OBJECTIVE:Cranial irradiation frequently results in growth hormone (GH) deficiency. Patients with radiation-induced GH deficiency usually remain responsive to exogenous growth hormone releasing hormone, implying radiation damages the hypothalamus rather than the pituitary. Little is known about the effect of cranial ir...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Ogilvy-Stuart AL,Wallace WH,Shalet SM

    更新日期:1994-08-01 00:00:00

  • Changes in TNM stage, reoperation and 131-I ablation rate during the use of newer methods for the preoperative diagnosis of differentiated thyroid carcinoma.

    abstract:OBJECTIVE:To define and discuss the changes of important risk factors and TNM staging over the last 40 years in patients operated on for differentiated thyroid carcinoma (DTC), resulting from the introduction of newer sensitive diagnostic procedures in the preoperative evaluation of thyroid nodules. PATIENTS:We review...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Karga H,Mavroudis K,Giagourta I,Triantaphyllopoulou M,Ktena V,Kassi G,Veloutsou H,Papapetrou P

    更新日期:2012-02-01 00:00:00

  • Diagnostic performance of HMGA2 gene expression for differentiation of malignant thyroid nodules: A systematic review and meta-analysis.

    abstract:OBJECTIVE:The purpose of the current study was to investigate the diagnostic performance of high mobility group A2 (HMGA2) gene expression for differentiation of malignant thyroid nodules through a systematic review and meta-analysis. DESIGN:The MEDLINE/PubMed and EMBASE database, from the earliest available date of i...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章,meta分析


    authors: Kim BH,Kim SJ,Kim M,Lee SW,Jeong SY,Pak K,Kim K,Kim IJ

    更新日期:2018-12-01 00:00:00

  • Nocturnal melatonin secretion in thyroid disease and in obesity.

    abstract:OBJECTIVE:The purpose was to investigate whether the function of the pinealocytes is changed in patients with disturbed metabolic rate or in subjects with marked obesity. DESIGN:Venous blood was sampled every second hour between 1800 and 0800 h, and urine collected between 2200 and 0700 h. PATIENTS:Eight patients wit...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Röjdmark S,Berg A,Rössner S,Wetterberg L

    更新日期:1991-07-01 00:00:00

  • Skewed X chromosome inactivation in girls and female adolescents with autoimmune thyroid disease.

    abstract:OBJECTIVE:Skewed X chromosome inactivation (XCI) was associated with female predominance in adult autoimmune thyroid disease (ATD). In normal females, skewed XCI is increased with age. Whether early-onset skewed XCI is associated with childhood ATD remains unknown. This study aimed to determine XCI skewing in paediatri...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Santiwatana S,Mahachoklertwattana P,Limwongse C,Khlairit P,Pongratanakul S,Roothumnong E,Prangphan K,Choubtum L,Songdej D,Poomthavorn P

    更新日期:2018-12-01 00:00:00

  • Sleep apnoea and daytime sleepiness in acromegaly: relationship to endocrinological factors.

    abstract::Sleep history and pituitary function were studied and sleep polygraphy performed in 11 acromegalic patients before and after pituitary surgery. Excessive daytime sleepiness or habitual snoring or both together, as well as an elevated fasting level of serum GH occurred in all the patients. In five men but in none of th...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Pekkarinen T,Partinen M,Pelkonen R,Iivanainen M

    更新日期:1987-12-01 00:00:00

  • Clearance and identification of thyrotrophin releasing hormone in human urine after intravenous injections.

    abstract::The urine clearance of TRH after intravenous injection in man has been measured by radioimmunoassay. Between 4.4 percent and 10.7 percent of the dose was excreted within 90 min, the majority within 30 min. The TRH excreted was immunochemically and chromatographically indistinguishable from synthetic TRH and was inacti...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Jeffcoate SL,White N

    更新日期:1975-07-01 00:00:00

  • Fertility induction in hypogonadotropic hypogonadal men.

    abstract::Men with hypogonadotropic hypogonadism (HH) are typically azoospermic, and yet HH is one of the few treatable forms of male infertility. Sperm induction protocols using gonadotrophins aim to replicate the natural endocrine control of spermatogenesis. Previously virilised men with adult-onset HH and normal testicular v...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章,评审


    authors: Prior M,Stewart J,McEleny K,Dwyer AA,Quinton R

    更新日期:2018-12-01 00:00:00

  • The corticotropin-releasing hormone test in the diagnosis of ACTH-dependent Cushing's syndrome: a reappraisal.

    abstract:OBJECTIVE:Stimulation with corticotropin-releasing hormone (CRH) is one of principal tools for the differential diagnosis of ACTH-dependent Cushing's syndrome. However, different dosages and species of CRH may be employed; further, ACTH levels can be measured by radioimmunoassay (RIA) or immunoradiometric assay (IRMA)....

    journal_title:Clinical endocrinology

    pub_type: 杂志文章,多中心研究


    authors: Pecori Giraldi F,Invitti C,Cavagnini F,Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-pituitary-adrenal axis.

    更新日期:2001-05-01 00:00:00

  • Prolactinomas in adolescents: persistent bone loss after 2 years of prolactin normalization.

    abstract:OBJECTIVE:To evaluate the effect of hyperprolactinaemia and its treatment with dopamine-agonists on bone mass and turnover in adolescent patients compared to adults. PATIENTS:Forty patients with hyperprolactinaemia (20 with disease onset during adolescence and 20 during adulthood) and 40 healthy control subjects. DES...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Colao A,Di Somma C,Loche S,Di Sarno A,Klain M,Pivonello R,Pietrosante M,Salvatore M,Lombardi G

    更新日期:2000-03-01 00:00:00

  • Calcium and parathyroid hormone behaviour after exogenous secretin infusion in man.

    abstract::The response of serum calcium, PTH, CT and gastrin to an infusion of secretin (3 CU/kg/h) over a period of 90 min was studied in ten healthy males and two female patients with hypoparathyroidism. In the healthy males serum calcium, after a transient fall, significantly increased at 45 min after the onset of the infusi...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Lo Cascio V,Piubello W,Cominacini L,Vantini I,Galvanini G,Ederle A,Cavallini G,Scuro LA

    更新日期:1982-04-01 00:00:00

  • In papillary thyroid carcinoma BRAFV600E is associated with increased expression of the urokinase plasminogen activator and its cognate receptor, but not with disease-free interval.

    abstract:CONTEXT:It has been suggested that patients with papillary thyroid cancer (PTC) harbouring the BRAF(V600E) mutation have a worse prognosis. We showed in PTC that high levels of urokinase plasminogen activator (uPA) and its cognate receptor (uPAR) inversely correlate with disease-free interval (DFI). OBJECTIVES:To inv...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Ulisse S,Baldini E,Sorrenti S,Barollo S,Prinzi N,Catania A,Nesca A,Gnessi L,Pelizzo MR,Mian C,De Vito C,Calvanese A,Palermo S,Persechino S,De Antoni E,D'Armiento M

    更新日期:2012-11-01 00:00:00

  • Features of papillary thyroid microcarcinoma associated with lateral cervical lymph node metastasis.

    abstract:OBJECTIVES:Papillary thyroid microcarcinoma (PTMC) has an excellent prognosis with an indolent disease course. However, some PTMCs have an aggressive course with lateral cervical lymph node (LCLN) metastasis or distant metastasis. This study aimed to evaluate the pre-operative features of PTMC associated with LCLN meta...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Jeon MJ,Chung MS,Kwon H,Kim M,Park S,Baek JH,Song DE,Sung TY,Hong SJ,Kim TY,Kim WB,Shong YK,Lee JH,Kim WG

    更新日期:2017-06-01 00:00:00

  • Prevalence of hypocalcaemia and its associated features in 22q11·2 deletion syndrome.

    abstract:BACKGROUND:22q11.2 deletion syndrome (22q11.2DS) is a relatively common yet under-recognized genetic syndrome that may present with endocrine features. We aimed to address the factors that contribute to the high prevalence of hypocalcaemia. METHODS:We investigated hypocalcaemia in a well-characterized sample of 138 ad...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章


    authors: Cheung EN,George SR,Costain GA,Andrade DM,Chow EW,Silversides CK,Bassett AS

    更新日期:2014-08-01 00:00:00

  • Radioiodine treatment for benign thyroid diseases.

    abstract::Radioiodine has been in use for over 60 years as a treatment for hyperthyroidism. Major changes in clinical practice have occurred with the realization that accurate dosimetry is incapable of avoiding the risks of hypothyroidism, while more accurate assessment of the risks of other adverse effects of radioiodine such ...

    journal_title:Clinical endocrinology

    pub_type: 杂志文章,实务指引


    authors: Weetman AP

    更新日期:2007-06-01 00:00:00