A compound heterozygous mutation in SLC34A3 causes hereditary hypophosphatemic rickets with hypercalciuria in a Chinese patient.
A compound heterozygous mutation in SLC34A3 causes hereditary hypophosphatemic rickets with hypercalciuria in a Chinese patient.
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SLC34A3 的复合杂合突变导致一名中国患者患有遗传性低磷血症性佝偻病并伴有高钙尿症。
DOI：
10.1016/j.bone.2013.11.008
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发表时间：
2014-02
期刊：
影响因子：
4.1
通讯作者：
Xia, Weibo
中科院分区：
文献类型：
--
作者：
Sun, Andrew Y;Zhou, Xueying;Meng, Xunwu;Xia, Weibo
遗传性低磷血症性佝偻病伴高钙尿症（HHRH）是一种罕见的常染色体隐性遗传性代谢紊乱，以低磷血症、身材矮小、佝偻病和/或骨软化症以及继发性吸收性高钙尿症为特征。HHRH最近被定位于染色体9 q34，其包含编码肾近端小管钠-磷酸盐协同转运蛋白NaPi-IIc的基因SLC 34 A3。我们报告一位29岁男性，有儿童佝偻病病史，表现为肾磷酸盐清除率增加，导致低磷酸盐血症、高钙尿、血清甲状旁腺激素（PTH）降低、血清1，25-二羟维生素D（1，25（OH）2D）升高和肾结石复发。我们对先证者及其父母的SLC 34 A3（外显子和相邻内含子）进行了突变分析，以确定是否存在遗传贡献。先证者被证明是SLC 34 A3中两个错义突变的复合杂合子：一个外显子7 c.571G>C（p.G191R）的新突变和一个先前鉴定的外显子13 c.1402C>T（p.R468W）的突变。他的父母都是这两种突变之一的无症状杂合子携带者。我们还进行了口服磷酸盐负荷试验，并比较了该患者与其他形式的低磷血症性佝偻病患者的血清磷酸盐、完整PTH和完整成纤维细胞生长因子23（iFGF 23），其结果进一步揭示了HHRH中低磷血症的机制与FGF 23无关。这是中国人群中HHRH的首次报告。我们在外显子7中发现的新突变增加了SLC 34 A3的20多个已报道的突变。
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder inherited in an autosomal recessive fashion and characterized by hypophosphatemia, short stature, rickets and/or osteomalacia, and secondary absorptive hypercalciuria. HHRH was recently mapped to chromosome 9q34, which contains the gene SLC34A3 which encodes the renal proximal tubular sodium–phosphate cotransporter NaPi-IIc. Here we describe a 29-year-old man with a history of childhood rickets who presented with increased renal phosphate clearance leading to hypophosphatemia, hypercalciuria, low serum parathyroid hormone (PTH), elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and recurrent nephrolithiasis. We performed a mutation analysis of SLC34A3 (exons and adjacent introns) of the proband and his parents to determine if there was a genetic contribution. The proband proved to be compound heterozygous for two missense mutations in SLC34A3: one novel mutation in exon 7 c.571G>C (p.G191R) and one previously identified mutation in exon 13 c.1402C>T (p.R468W). His parents were both asymptomatic heterozygous carriers of one of these two mutations. We also performed an oral phosphate loading test and compared serum phosphate, intact PTH, and intact fibroblast growth factor 23 (iFGF23) in this patient versus patients with other forms of hypophosphatemic rickets, the results of which further revealed that the mechanism of hypophosphatemia in HHRH is independent of FGF23. This is the first report of HHRH in the Chinese population. Our findings of the novel mutation in exon 7 add to the list of more than 20 reported mutations of SLC34A3.
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DOI：
10.1016/s0084-3741(08)70143-4
发表时间：
2007
期刊：
Yearbook of Endocrinology
影响因子：
--
作者：
B. Clarke
通讯作者：
B. Clarke
影响因子：
4.1
作者：
Braithwaite V;Pettifor JM;Prentice A
通讯作者：
Prentice A
DOI：
10.1152/ajprenal.00090.2008
发表时间：
2008-08-01
影响因子：
4.2
作者：
Jaureguiberry, Graciana;Carpenter, Thomas O.;Bergwitz, Clemens
通讯作者：
Bergwitz, Clemens
影响因子：
6.2
作者：
H. Tenenhouse
通讯作者：
H. Tenenhouse
影响因子：
19.6
作者：
Nishida, Y.;Taketani, Y.;Takeda, E.
通讯作者：
Takeda, E.