PDF(Pubmed)
Abstract：
BACKGROUND: This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence, featuring a unique mutation in the peroxisome proliferator-activated receptor gamma (PPARG) gene. Data Access Statement: Research data supporting this publication are available from the NN repository at www.NNN.org/download/.
METHODS: The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family members. Additionally, high-throughput sequencing was conducted to analyze the PPARG genes of the patient, her siblings, and their offspring. The results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy, accompanied by insulin resistance and hypertriglyceridemia. Furthermore, these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation patterns. The results from the gene detection process demonstrated a heterozygous mutation of guanine (G) at position 284 in the coding region of exon 2 of PPARG, which replaced the base adenine (A) (exon2c.284A>Gp.Tyr95Cys). This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated protein. Notably, both of her siblings harbored a nucleotide heterozygous variation at the same site, and both were diagnosed with diabetes.
CONCLUSIONS: The PPARG gene mutation, particularly the p.Tyr95Cys mutation, may represent a newly identified subtype of maturity-onset diabetes of the young. This subtype is characterized by insulin resistance and lipid metabolism disorders.
METHODS: The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family members. Additionally, high-throughput sequencing was conducted to analyze the PPARG genes of the patient, her siblings, and their offspring. The results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy, accompanied by insulin resistance and hypertriglyceridemia. Furthermore, these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation patterns. The results from the gene detection process demonstrated a heterozygous mutation of guanine (G) at position 284 in the coding region of exon 2 of PPARG, which replaced the base adenine (A) (exon2c.284A>Gp.Tyr95Cys). This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated protein. Notably, both of her siblings harbored a nucleotide heterozygous variation at the same site, and both were diagnosed with diabetes.
CONCLUSIONS: The PPARG gene mutation, particularly the p.Tyr95Cys mutation, may represent a newly identified subtype of maturity-onset diabetes of the young. This subtype is characterized by insulin resistance and lipid metabolism disorders.
摘要：
背景：这项研究提出了在青春期发生的成人发病糖尿病的罕见病例的临床和基因突变特征，具有过氧化物酶体增殖物激活受体γ（PPARG）基因的独特突变。数据访问声明：支持本出版物的研究数据可从www上的NN存储库中获得。NNN.org/download/.
方法：所采用的方法需要从先证者及其各自的家庭成员中仔细收集全面的临床数据。此外,进行高通量测序以分析患者的PPARG基因，她的兄弟姐妹,和他们的后代。这项调查的结果表明，患者最初在怀孕期间表现出升高的血糖水平，伴有胰岛素抵抗和高甘油三酯血症。此外，这些菌株对糖尿病肾病的易感性增加,且没有任何明显的聚集模式.基因检测过程的结果表明，鸟嘌呤（G）在PPARG外显子2编码区的284位发生杂合突变，它取代了碱基腺嘌呤(A)(exon2c.284A>Gp。Tyr95Cys）。这种错义突变导致酪氨酸在翻译蛋白的第95位被半胱氨酸取代。值得注意的是,她的两个兄弟姐妹在同一位点都有一个核苷酸杂合变异，两人都被诊断出患有糖尿病。
结论：PPARG基因突变，尤其是p.Tyr95Cys突变,可能代表了一种新发现的青少年成熟型糖尿病亚型。该亚型的特征在于胰岛素抵抗和脂质代谢紊乱。
方法：所采用的方法需要从先证者及其各自的家庭成员中仔细收集全面的临床数据。此外,进行高通量测序以分析患者的PPARG基因，她的兄弟姐妹,和他们的后代。这项调查的结果表明，患者最初在怀孕期间表现出升高的血糖水平，伴有胰岛素抵抗和高甘油三酯血症。此外，这些菌株对糖尿病肾病的易感性增加,且没有任何明显的聚集模式.基因检测过程的结果表明，鸟嘌呤（G）在PPARG外显子2编码区的284位发生杂合突变，它取代了碱基腺嘌呤(A)(exon2c.284A>Gp。Tyr95Cys）。这种错义突变导致酪氨酸在翻译蛋白的第95位被半胱氨酸取代。值得注意的是,她的两个兄弟姐妹在同一位点都有一个核苷酸杂合变异，两人都被诊断出患有糖尿病。
结论：PPARG基因突变，尤其是p.Tyr95Cys突变,可能代表了一种新发现的青少年成熟型糖尿病亚型。该亚型的特征在于胰岛素抵抗和脂质代谢紊乱。
