在患有偏偏甲状腺症的患者中发现PTH基因的两种新鲜罕见变异
Yue Jiang1, An Song1, Jiajia Wang1
1Department of Endocrinology, Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Osteoporosis and sarcopenia
|April 21, 2025
概括
在患有家族隔离性甲状腺功能低下症 (FIH) 的患者中,发现了甲状腺侧腺激素 (PTH) 基因的两种新鲜罕见变异. 这些变种会损害PTH激素的分泌,扩大FIH已知的遗传原因.
科学领域:
- 内分泌学 在内分泌学.
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 甲状腺功能低下症 (HP) 是一种罕见的内分泌疾病,由甲状腺类激素 (PTH) 缺乏引起.
- PTH基因是家族隔离性甲状腺功能低下症 (FIH) 的关键候选者.
研究的目的:
- 调查PTH基因中两个新鲜罕见变异 (RVs) 的致病性.
- 阐明这些变异对PTH合成和分泌的功能影响.
主要方法:
- 利用目标下一代测序来识别PTH基因突变.
- 在实验室进行的功能研究,使用局部导向的突变发生和细胞转染.
- 测量了完整的PTH (iPTH) 和PTH (1-84) 水平,并通过西式涂抹评估了蛋白质表达.
主要成果:
- 在患有偏偏甲状腺症的患者中发现了两种新的PTH变异 (p.Val52Ile和p.Leu90Phe).
- 与野生型 (WT) 相比,突变的PTH变体显著降低了IPTH和PTH (1-84) 的分泌量 (P <0.05).
- 观察到的激素分泌的减少并没有被4-酸 (4-PBA) 挽救,细胞内PTH水平保持不变.
结论:
- 在PTH基因 (Val52Ile和Leu90Phe) 中有两种新奇罕见变异会损害激素的合成和分泌.
- 这些发现扩大了与FIH相关的PTH基因的突变谱.
- 这项研究提供了关于家族隔离性甲状腺功能低下症潜在机制的见解.
相关概念视频
Comparing Copy Number Variations and SNPs
16.7K
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
16.7K
Single Nucleotide Polymorphisms-SNPs
13.6K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
13.6K
Pleiotropy
37.9K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
37.9K
Histone Variants at the Centromere
4.3K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
4.3K
Incomplete Dominance
20.3K
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
20.3K
X-linked Traits
51.5K
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
51.5K


