Clinical and molecular genetic characteristics of patients with hereditary hypophosphatemia

苯丙氨酸 低磷血症 低磷血症性佝偻病 多重连接依赖探针扩增 医学 内科学 内分泌学 基因 遗传学 生物 佝偻病 维生素D与神经学 外显子
作者
Mehmet Eltan,Ceren Alavanda,Zehra Yavaş Abalı,Büşra Gürpınar Tosun,İlknur Kurt,Tarık Kırkgöz,Serçin Güven,Sare Betül Kaygusuz,Saygın Abalı,Didem Helvacıoğlu,Tülay Güran,İbrahim Gökçe,Ahmet Arman,Abdullah Bereket,Pınar Ata,Serap Turan
出处
期刊:The Journal of Clinical Endocrinology and Metabolism [Oxford University Press]
标识
DOI:10.1210/clinem/dgae868
摘要

Abstract Background Hereditary hypophosphatemia (HH), is a rare condition related to decreased renal tubular phosphate reabsorption. Although X-linked hypophosphatemia or PHEX gene variant is the most frequent cause of HH, recent advances in next-generation sequencing (NGS) techniques enable the identification of genetic etiologies as a whole. Objective To identify genetic causes of HH using various genetic testing methods and to compare clinical features between FGF23-dependent and FGF23-independent HH groups. Design and Methods Fifty patients (24 males) from 39 unrelated families were included. Based on initial evaluation, PHEX gene sequencing was performed in patients with clinical and biochemical findings suggestive of FGF23-dependent HH. If sequencing showed no alterations, multiplex ligation-dependent probe amplification (MLPA) analysis for PHEX was conducted. Initially, a specific gene panel was performed for FGF23-independent HH or those in whom PHEX gene showed no genetic alteration. Results Genetic etiology was revealed in 43 patients from 33 families. PHEX gene variants were identified (four novel) in 24 patients from 19 unrelated families (50%). SLC34A3 was the second most common (16.6%) and the rest were rarer causes of hypophosphatemia (DMP1 n=3, SLC34A1 n=2, CLCN5 n=2, OCRL n=2, FAM2°C n=1, SLC2A2 n=1). When the genetically proven FGF23-dependent (n=28) and FGF23-independent (n=15) HH groups were compared for clinical and biochemical features; lower phosphate and TmP/GFR SDSs and higher ALP SDS with more severe clinical rickets were detected in FGF23-dependent group, whereas, higher serum and urine calcium and lower PTH levels were detected in FGF23-independent group. Conclusions The application of MLPA provided an additional explanatory value of 10% to the molecular etiology. However, 10% of the cases of HH still remain unexplained even after a comprehensive genetic work-up. Biochemical findings suggest distinct biochemical profiles between FGF23-dependent and FGF23-independent HH groups.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
1秒前
大模型应助Du采纳,获得10
1秒前
1秒前
自觉的傲薇应助hyominhsu采纳,获得10
1秒前
1秒前
哒哒发布了新的文献求助10
2秒前
66完成签到,获得积分10
2秒前
zheng能量完成签到,获得积分10
3秒前
hao完成签到,获得积分10
3秒前
3秒前
Survivor完成签到,获得积分10
4秒前
淡然枫完成签到,获得积分10
4秒前
4秒前
4秒前
茉莉猫哟发布了新的文献求助10
4秒前
4秒前
王鹏飞应助lemon采纳,获得10
4秒前
5秒前
5秒前
koko完成签到,获得积分10
5秒前
5秒前
852应助WIN1016采纳,获得10
6秒前
阿柒完成签到,获得积分10
6秒前
鳄鱼蛋发布了新的文献求助10
6秒前
ddd发布了新的文献求助10
6秒前
JamesPei应助传统的钧采纳,获得10
6秒前
6秒前
ding应助feiCheung采纳,获得10
6秒前
7秒前
qiu完成签到,获得积分10
7秒前
yuqinghui98发布了新的文献求助10
7秒前
yue发布了新的文献求助10
7秒前
量子星尘发布了新的文献求助10
7秒前
Lion完成签到,获得积分20
7秒前
贪玩的甜瓜完成签到,获得积分10
7秒前
漂亮孤兰完成签到 ,获得积分10
7秒前
8秒前
8秒前
大模型应助落后的哈密瓜采纳,获得10
8秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3969398
求助须知:如何正确求助?哪些是违规求助? 3514239
关于积分的说明 11173064
捐赠科研通 3249531
什么是DOI,文献DOI怎么找? 1794934
邀请新用户注册赠送积分活动 875501
科研通“疑难数据库(出版商)”最低求助积分说明 804827