Wang Chenglin
Department of Endocrinology, Shanxi Provincial People's Hospital, Taiyuan, China.
Front Genet. 2025 May 23;16:1541946. doi: 10.3389/fgene.2025.1541946. eCollection 2025.
To screen for possible pathogenic mutations in polycystic ovary syndrome (PCOS) patients with diabetes and preliminarily explore the relationship between genotype and phenotype to offer a research basis for PCOS pathogenesis with diabetes.
Four patients with PCOS and diabetes were recruited and their demographic and clinical data were collected. Genomic DNA was extracted from peripheral blood leukocytes of the study subjects. High-throughput whole-exome sequencing was conducted to identify candidate genes that could play a pathogenic role in PCOS with diabetes in Aiji Taikang. The sequencing data obtained were evaluated using a variety of bioinformatics tools. Verification of candidate sites was done by Sanger sequencing.
Based on whole-exome sequencing, six mutations residing in three genes were detected in these four patients: (1) located at Chr 3q29, (2) FSHD region gene 1 ()gene located at Chr 4q35.2, and (3) androgen receptor () located at Chr Xq11-q12 were detected in these four patients (every patients had the 6 mutations). Of the six genetic mutations, an insertion/deletion (indel) mutation was found in the mucin 4 () gene [MUC4:NM_018406.6:2/25:c.7701_7702insTCAGTATCCACAGGTCATGCCACCCCTCTTCATGTCACCGACACTTCC:p.(Ser2567_Ala2568insSerValSerThrGlyHisAlaThrProLeuHisValThrAspThrSer)], and an indel mutation in the gene (:NM_000044:exon1:c.173_174insGCAGCA:p. Q58delinsQQQ), while the other four were missense single-nucleotide polymorphisms (SNPs) located in of uncertain significance (:NM_004477:exon8:c.T692C:p. L231P, :NM_004477:exon8:c.C728T:p.T243M, :NM_004477:exon8:c.C733A:p.L245M, FRG1:NM_004477:exon8:c.T734G:p.L245R). A Mucin 4 () gene indel mutation was detected at the same site in four patients, which could be associated with endometriosis-related infertility. The gene indel mutation, :NM_000044:exon1:c.173_174insGCAGCA: p. Q58delinsQQQ was detected simultaneously in four patients.
Whole exome sequencing can quickly identify candidate genes for genes. Gaining an in-depth understanding of the AR mutations underlying PCOS with diabetes will deepen our understanding of the endocrine factors involved in the disease etiology, and provide potential targets for treatment.
筛选多囊卵巢综合征（PCOS）合并糖尿病患者可能的致病突变，初步探索基因型与表型的关系，为PCOS合并糖尿病的发病机制提供研究依据。
招募4例PCOS合并糖尿病患者，收集其人口统计学和临床资料。从研究对象的外周血白细胞中提取基因组DNA。进行高通量全外显子测序，以鉴定在爱基泰康可能对PCOS合并糖尿病起致病作用的候选基因。使用多种生物信息学工具对获得的测序数据进行评估。通过桑格测序对候选位点进行验证。
基于全外显子测序，在这4例患者中检测到位于3个基因的6个突变：（1）位于3号染色体长臂29区，（2）位于4号染色体长臂35.2区的FSHD区域基因1（）基因，以及（3）位于X染色体长臂11 - 12区的雄激素受体（）在这4例患者中均被检测到（每位患者均有这6个突变）。在这6个基因突变中，在粘蛋白4（）基因[MUC4:NM_018406.6:2/25:c.7701_7702insTCAGTATCCACAGGTCATGCCACCCCTCTTCATGTCACCGACACTTCC:p.(Ser2567_Ala2568insSerValSerThrGlyHisAlaThrProLeuHisValThrAspThrSer)]中发现一个插入/缺失（indel）突变，在基因（:NM_000044:exon1:c.173_174insGCAGCA:p. Q58delinsQQQ）中发现一个indel突变，而另外4个是位于意义不明确的（:NM_004477:exon8:c.T692C:p. L231P，:NM_004477:exon8:c.C728T:p.T243M，:NM_004477:exon8:c.C733A:p.L245M，FRG1:NM_004477:exon8:c.T734G:p.L245R）中的错义单核苷酸多态性（SNP）。在4例患者的同一位置检测到粘蛋白4（）基因indel突变，这可能与子宫内膜异位症相关的不孕有关。基因indel突变，:NM_000044:exon1:c.173_174insGCAGCA: p. Q58delinsQQQ在4例患者中同时被检测到。
全外显子测序可快速鉴定基因的候选基因。深入了解PCOS合并糖尿病潜在的AR突变将加深我们对该疾病病因中涉及的内分泌因素的理解，并为治疗提供潜在靶点。
