Lam, KSL

Lo, CY

Rong, R

Tan, KCB

Teh, BT

Tiu, SC

Tso, AWK

Wat, NMS

Xu, JY

Hong Kong Medical Journal

HKU Scholars Hub

Title The clinical genetics of multiple endocrine neoplasia type 1 inChineseAuthor(s) Rong, R; Tso, AWK; Lo, CY; Tan, KCB; Tiu, SC; Wat, NMS; Xu,JY; Teh, BT; Lam, KSLCitationThe 8th Medical Research Conference, Medical Science Group,The University of Hong Kong, Queen Mary Hospital, Hong Kong,25-26 January 2003, v. 9 n. 1 Suppl, p. 33Issued Date 2003URL http://hdl.handle.net/10722/54148Rights Creative Commons: Attribution 3.0 Hong Kong LicenseHKMJ Vol 9 No 1 February 2003 Supplement      33The clinical genetics of multiple endocrine neoplasia type 1 in ChineseR. Rong1, A.W.K. Tso1, C.Y. Lo2, K.C.B. Tan1, S.C. Tiu3, N.M.S. Wat1, J.Y. Xu1, B.T. Teh4 and K.S.L. Lam1.1Department of Medicine, 2 Department of Surgery, University of Hong Kong; 3 Department of Medicine, Queen ElizabethHospital, Hong Kong; 4Laboratory of Cancer Genetics, Van Andel Research Institue, Grand Rapids, USA.Introduction : Multiple endocrine neoplasia type 1 (MEN 1) is characterized by a triad of neoplasia affecting theparathyroid glands, enteropancreatic endocrine tissue and the anterior pituitary gland.Methods : In order to define the prevalence of MEN 1 germ-line mutations in Southern Chinese patients with MEN1 syndrome, we performed direct sequencing of the entire open reading frame of the MEN1 gene for twelve indexpatients and their first degree relatives.Results : Six patients had familial MEN 1 syndrome and six had sporadic disease. Nine different germ-line muta-tions at the MEN1 gene were identified, including three novel mutations (248-249delTT in exon 2, K559X(AAG→TAG) in exon 10 and IVS 2nt+2(G→T) in intron 2). All patients with familial MEN 1 syndrome wereheterozygous carriers of a germ-line mutation and MEN 1-related disorders were only evident in their first-degreerelatives who also carried the mutation. All patients with enteropancreatic lesion were mutation carriers and theabsence of mutation in three apparently sporadic MEN 1 patients with only hyperparathyroidism and pituitarymicroadenoma might represent the presence of MEN1 phenocopy.Conclusions : The finding of MEN1 germ-line mutation in all patients with familial MEN 1 syndrome suggests thatgenetic screening should be useful in our population to identify affected individuals within a kindred and allowearly detection of MEN1-related tumours.Acknowledgement : This work is supported by CRGC Grant, University of Hong KongThe effect of dietary caloric density on neuropeptide response in miceAWK Tso1, G Segal-Lieberman2, E Kokkotou2, N Tritos2, E Maratos-Flier2Department of Medicine, Queen Mary Hospital, Hong Kong1 ; Obesity Section, Joslin Diabetes Center and Harvard MedicalSchool, Boston, Massachusetts 02215, U.S.A.2Introduction : Hypothalamic neuropeptides, such as pro-opiomelanocortin (POMC), an anorectic peptide andneuropeptide Y (NPY), an orexigenic peptide, play key roles in the regulation of energy balance. The regulation oftheir expressions may be important in determining susceptibility to diet-induced obesity.Methods : Three strains of mice (C57BL/6J, 129/Sv and A/J) known to have different susceptibilities to diet-induced obesity were used. They were fed a 23.6% fat, w/w, high fat diet (HF) or a 4.3% low fat control diet for twodays. In the second experiment, four groups of each strain of mice were placed on diets with different fat contentsand caloric densities for a period of six weeks. In both experiments, neuropeptide mRNA expression was measuredusing real-time quantitative reverse transcription polymerase chain reaction (RT-PCR).Results : The weight gain of the mice over 6 weeks correlated with the caloric density rather than the fat content ofthe diets. A differential weight gain was observed between strains with C57BL/6J having the lowest threshold indeveloping obesity, suggesting an influence of susceptibility genes. On acute exposure to a high caloric densitydiet, C57BL/6J had a paradoxical rise in hypothalamic NPY expression (p<0.01) despite a trend to higher caloricintake. After six weeks on diets with increasing caloric density, both C57BL/6J and 129/Sv developed significantsuppression in POMC expression compared to those on control diets (p<0.05) despite the presence ofhyperleptinaemia. In contrast, the least obesity-prone A/J mice mounted a rise in POMC expression on acute expo-sure to a high caloric density diet (p<0.05) and maintained POMC expression even after prolonged exposure.Conclusions : It is proposed that an acute rise in POMC expression in response to a high fat challenge may be apredictor of low susceptibility to adiposity. The dysregulation of POMC neurons in response to high caloric intakemay be important in mediating diet-induced obesity.Acknowledgement : This work is supported by NIH grant (NIH 1RO1DK56113-01)EM-05EM-06

The clinical genetics of multiple endocrine neoplasia type 1 in Chinese

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The clinical genetics of multiple endocrine neoplasia type 1 in Chinese

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