"De Novo"男性2综合征的患病率和遗传学
Roberta Casalini1, Cristina Romei1, Valeria Bottici1
1Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy.
The Journal of clinical endocrinology and metabolism
|March 25, 2025
概括
大约16%的遗传性骨髓性甲状腺癌 (MTC) 病例是由新发RET突变引起的,主要是来自父亲. 这些de novo突变可能发生在精子发育过程中,而父亲的晚年是潜在的贡献因素.
科学领域:
- 遗传学 是一个遗传学.
- 内分泌学 在内分泌学.
- 癌症生物学 癌症生物学
背景情况:
- 遗传性髓性甲状腺癌 (MTC) 占MTC病例的25%.
- 生殖线RET突变导致遗传MTC,产生的遗传或新的.
- 遗传学和新发多发性内分泌新陈代谢2型 (MEN2) 综合征的患病率尚未完全理解.
研究的目的:
- 为了确定新出现的MEN2综合征的流行率和遗传基础.
- 为了调查 de novo RET 突变的父母起源.
- 描述在生殖线传播期间发生的新型RET突变的发生情况.
主要方法:
- 对152个家族遗传性MTC的分析.
- 在索引病例和父母中测序野生类型和突变的RET等位基因.
- 单核酸多态性 (SNP) 分析,以确定等位基因的起源.
- 数字滴滴PCR (ddPCR) 用于检测索引病例和父母中的马赛克.
主要成果:
- 在遗传MTC家族中的15.78% (24/152) 发现了de novo RET突变.
- 所有的de novo突变都是来自父亲的.
- 缺少马赛克主义表明在精子生成过程中发生了突变.
- 在一些,但不是所有,de novo案例中观察到晚年父亲年龄.
结论:
- 新生遗传性MEN2综合征的患病率约为16%,表型之间存在差异.
- 在MTC中所有de novo RET突变都是来自父亲的,可能是在精子DNA形成期间获得的.
- 晚年父亲的年龄可能会导致de novo RET突变的发生,尽管没有得到确定的证据.
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相关概念视频
Pedigree Analysis
Overview
Sex-linked Disorders
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
Nondisjunction
During meiosis, chromosomes occasionally separate improperly. This occurs due to failure of homologous chromosome separation during meiosis I or failed sister chromatid separation during meiosis II. In some species, notably plants, nondisjunction can result in an organism with an entire additional set of chromosomes, which is called polyploidy. In humans, nondisjunction can occur during male or female gametogenesis and the resulting gametes possess one too many or one too few chromosomes.
Genomic Imprinting and Inheritance
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
Incomplete Dominance
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.
Nondisjunction
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold sister...
