一个深内含子PHEX变异在一个大的丹麦家族遗传性低磷血症和轻度骨骼,但更严重的牙齿表型。

IF 3.6
Bone Pub Date : 2025-10-01 DOI:10.1016/j.bone.2025.117666
Jenny Blechingberg, Kristian Alsbjerg Skipper, Signe Sparre Beck-Nielsen, Pernille Axél Gregersen
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引用次数: 0

摘要

遗传性低磷血症(HH)是一种罕见的疾病,其特征是过度的肾磷酸盐消耗、佝偻病和成长期儿童骨软化症以及成人骨软化症。有几种类型的HH是由许多不同基因的致病变异引起的。我们提出了一个由19个家庭成员组成的丹麦大家庭,其临床和生化低磷血症是由先前未报道的PHEX深内含子剪接变异引起的:c.1080-687 a > G (p.?)。与其他疾病引起的PHEX变异个体相比,受影响的家庭成员表现出较轻的HH表型。通过基因组测序内含子分析和体外外显子捕获分析,我们能够从遗传学上确认x连锁低磷血症(XLH)的诊断。我们的研究结果强调了XLH的表型变异性,这个家族通常表现出较温和的表型。此外,我们的研究结果表明XLH可能是由PHEX的内含子变异引起的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A deep intronic PHEX variant in a large Danish family with hereditary hypophosphatemia and a milder skeletal, but more severe dental phenotype.

Hereditary hypophosphatemia (HH) are rare diseases, characterized by excessive renal phosphate wasting, rickets and osteomalacia in growing children, and osteomalacia in adults. There are several types of HH caused by pathogenic variants in a number of different genes. We present a large Danish family consisting of 19 family members with clinically and biochemically hypophosphatamia caused by a previously unreported deep intronic splice variant in PHEX: c.1080-687 A > G (p.?). The affected family members displayed a milder HH phenotype compared with a larger group of individuals with other disease causing PHEX variants. We were able to genetically confirm a diagnosis of X-linked hypophosphatemia (XLH) by genome sequencing intron analysis and in vitro analysis consisting of an exon trapping assay. Our findings emphasize the phenotypic variability of XLH, where this family in general displays a milder phenotype. Furthermore, our findings demonstrate that XLH can be caused by intron variants in PHEX.

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