近日，國家重點學(xué)科中山大學(xué)內(nèi)分泌學(xué)科帶頭人中山大學(xué)附屬第三醫(yī)院翁建平教授的科研團隊發(fā)現(xiàn)了我國大陸首例特殊類型糖尿病MODY2家系,，并在遺傳學(xué)發(fā)現(xiàn)了新的突變位點,，相關(guān)結(jié)果發(fā)表在《人類遺傳學(xué)》（Human Genetics）雜志（Hum Genet 2011,129(3):231- 238.）。
在該研究中,，翁教授指導(dǎo)下的遺傳課題組沈云峰博士報道了中國大陸首個青少年中的成年起病型糖尿病II型（MODY2）家系,，該家系表現(xiàn)為常染色體顯性遺傳，所有患者均存在空腹高血糖,，且基礎(chǔ)狀態(tài)下胰島素分泌減少,。基因測序提示該家系高血糖患者均存在一個新的葡萄糖激酶（GCK）基因突變—E339K（谷氨酸→賴氨酸）,，突變與高血糖共分離,。為明確突變與高血糖的因果關(guān)系，該研究進行了進一步的突變基因功能學(xué)研究,，結(jié)果表明突變造成的GCK酶活性與熱穩(wěn)定性顯著下降可能是其引起高血糖的具體機制,。
在本研究前，中國大陸項坤三院士報道過MODY5家系（Acta Diabetol. 2004;41(4):137-45）,。而本研究的貢獻在于發(fā)現(xiàn)中國的大陸地區(qū)首個MODY2家系,，首次報道了MODY-2新的突變位點E339K，并從功能學(xué)上部分闡釋了基因點突變和高血糖的因果關(guān)系,。
該項工作得到了教育部博士后研究基金（20060390754）,、教育部博士點基金（200805580070）、廣東省自然科學(xué)基金（8151008901000196）和廣東省醫(yī)學(xué)科學(xué)基金（B2008045）的資助,。（生物谷Bioon.com）
生物谷推薦原文出處：
Hum Genet. 2011 Mar;129(3):231-8. Epub 2010 Nov 23.
Insight into the biochemical characteristics of a novel glucokinase gene mutation.
Shen Y, Cai M, Liang H, Wang H, Weng J.
Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-sen University, Research Center for Diabetes Care of Guangdong Province, 600 Tianhe Road, Guangzhou, 510630, Guangdong, People's Republic of China.
Abstract
Glucokinase (GCK) acts as a glucose sensor and regulates β-cell insulin secretion. The heterozygous mutations in the gene encoding GCK cause a reduction of the enzyme activity, which results in a monogenic form of diabetes, maturity-onset diabetes of the young. In the present study, we identified and functionally characterized a novel missense mutation in the GCK gene, which results in a protein mutation Glu(339) → Lys (E339K), from a Chinese family with hyperglycemia. The same GCK mutation that co-segregated with diabetes phenotype was identified in five members of this family but was not found in 200 healthy control individuals. We expressed and affinity-purified the GCK proteins from bacterial expression system that carries mutation (E339K) and fused to glutathione S-transferase. The expressed GCK protein was subjected to the measurement of its biochemical effects of the missense mutation on GCK activity. Our results showed that the mutation reduced the GCK protein yield. The enzymatic kinetics and the thermal stability analysis on the recombinant GCK proteins revealed that the mutation inactivates enzyme kinetics and severely impaired the GCK protein stability.
