儿童LRP5基因变异的临床,生物化学和放射学特征
Graziamaria Ubertini1, Danilo Fintini1, Francesco d'Aniello1
1Endocrinology and Diabetology Unit, IRCCS 'Bambino Gesù' Children's Hospital, Rome, Italy.
Calcified tissue international
|August 12, 2025
概括
低密度脂蛋白受体相关蛋白5 (LRP5) 基因中的遗传变异会导致儿童的骨质疏松症. 双酸盐治疗有效地改善了骨矿物质密度,并减少了儿科队列中骨折风险.
科学领域:
- 遗传学 遗传学 是一个
- 儿科内分泌学 儿科内分泌学
- 骨生物学 骨生物学
背景情况:
- 低密度脂蛋白受体相关蛋白5 (LRP5) 基因变异与原发性骨质疏松症和复发性骨折有关.
- 异性LRP5变体通常存在于从幼儿时期开始的骨质减少.
研究的目的:
- 描述患有LRP5基因变异的儿科患者的临床特征和治疗结果.
- 评估当前治疗方法在与LRP5变化相关的骨质疏松症管理中的有效性.
主要方法:
- 从7名儿科患者 (5名男性) 的临床数据进行了回顾性分析,这些患者具有已确定的LRP5变体.
- 基因测序,以识别LRP5基因中的异合体和复合异合体变体.
- 评估治疗结果,包括骨折发生率,骨矿物密度 (BMD) 和不良影响.
主要成果:
- 确定了8种异合体LRP5变体 (6种错误,2种无意义),其中2种被认为可能是致病性.
- 一名患有复合异合体变体的患者表现出严重的表型,类似于骨质疏松症-伪瘤综合征.
- 所有接受双酸盐或苏马布治疗的患者在随访期间都没有出现新的骨折.
- 观察到骨质量显著增加 (平均为55%) 和部分脊椎重塑.
结论:
- 在儿童中存在显著的表型变异的LRP5基因变异.
- 双酸盐疗法在改善骨损伤和减少儿科LRP5相关骨质疏松症中骨折风险方面是有效的.
- 对针对Wnt信号和LRP5受影响途径的精密疗法进行进一步的研究是有必要的.
相关概念视频
01:22Lysosomal Hydrolases
3.9K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.9K
02:41Lethal Alleles
15.7K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.7K
01:21Smooth Endoplasmic Reticulum
6.2K
Smooth endoplasmic reticulum or smooth ER is a sub-organelle with specialized functions in animal cells and plant cells. It is often associated with the tubule morphology of the endoplasmic reticulum.
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
6.2K
01:33Pleiotropy
41.1K
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,...
41.1K
01:31Translation
15.6K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
15.6K
01:20The Retinoblastoma Gene
4.2K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.2K