近日，国家重点学科中山大学内分泌学科带头人中山大学附属第三医院翁建平教授的科研团队发现了我国大陆首例特殊类型糖尿病MODY2家系，并在遗传学发现了新的突变位点，相关结果发表在《人类遗传学》（Human Genetics）杂志（Hum Genet 2011,129(3):231- 238.）。
在该研究中，翁教授指导下的遗传课题组沈云峰博士报道了中国大陆首个青少年中的成年起病型糖尿病II型（MODY2）家系，该家系表现为常染色体显性遗传，所有患者均存在空腹高血糖，且基础状态下胰岛素分泌减少。基因测序提示该家系高血糖患者均存在一个新的葡萄糖激酶（GCK）基因突变—E339K（谷氨酸→赖氨酸），突变与高血糖共分离。为明确突变与高血糖的因果关系，该研究进行了进一步的突变基因功能学研究，结果表明突变造成的GCK酶活性与热稳定性显著下降可能是其引起高血糖的具体机制。
在本研究前，中国大陆项坤三院士报道过MODY5家系（Acta Diabetol. 2004;41(4):137-45）。而本研究的贡献在于发现中国的大陆地区首个MODY2家系，首次报道了MODY-2新的突变位点E339K，并从功能学上部分阐释了基因点突变和高血糖的因果关系。
该项工作得到了教育部博士后研究基金（20060390754）、教育部博士点基金（200805580070）、广东省自然科学基金（8151008901000196）和广东省医学科学基金（B2008045）的资助。（生物谷Bioon.com）
生物谷推荐原文出处：
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.
