Novel SLC34A3 mutation causing hereditary hypophosphataemic rickets with hypercalciuria in a Gambian family.
Novel SLC34A3 mutation causing hereditary hypophosphataemic rickets with hypercalciuria in a Gambian family.
复制标题
DOI：
10.1016/j.bone.2012.12.003
复制
发表时间：
2013-03
期刊：
影响因子：
4.1
通讯作者：
Prentice A
中科院分区：
文献类型：
--
作者：
Braithwaite V;Pettifor JM;Prentice A
三个兄弟姐妹，年龄分别为12岁、4岁和2岁，在冈比亚的一家诊所出现骨畸形。膝盖和手腕的X光片证实了明显的佝偻病。对该家庭（包括2名未患病的兄弟姐妹和母亲）进行遗传性佝偻病调查。三个受影响的兄弟姐妹有遗传性低磷酸盐血症佝偻病伴高钙尿症（HHRH）的生化特征，血浆钙和25-羟维生素D浓度正常，1，25-二羟维生素D升高，低磷酸盐血症，高磷酸盐尿症和高钙尿症。在介绍中，三个受影响的兄弟姐妹中的两个具有升高的成纤维细胞生长因子-23（FGF 23）浓度。母亲和临床上未受影响的兄弟姐妹基本上具有正常的生物化学。在来自兄弟姐妹及其母亲的DNA样本中，对编码IIc型钠-磷酸盐协同转运蛋白的SLC 34 A3基因进行了遗传分析。结果发现3个单核苷酸多态性（SNPs）：S168 F、E513 V和L599 L。E513 V和L599 L先前已被鉴定为良性多态性。然而，S168 F是以前未报道的变体。计算机模拟突变评价预测，S168 F突变导致蛋白产物发生变化，从而损害其功能。此外，三个临床受影响的兄弟姐妹是纯合子的S168 F变异，而未受影响的家庭成员是运营商。这项研究描述了一个生化档案和互补基因数据一致的一种罕见的遗传性低磷酸盐血症佝偻病的家庭从农村冈比亚。据我们所知，这项研究报告了非洲的第一例HHRH病例，并描述了SLC 34 A3基因内的一种新的因果突变。一个冈比亚家庭，5名儿童，其中3名兄弟姐妹患有明显佝偻病，疑似HHRH，低磷酸盐血症的生化特征，尿磷酸盐和钙排泄升高。SLC 34 A3基因的遗传学分析表明S168 F是一个新的突变。③患病同胞为S168 F纯合子，未患病同胞为携带者。我们报告了非洲首例遗传性低磷酸盐血症性佝偻病伴高钙尿症。
Three siblings, aged 12, 4 and 2 years, presented at a Gambian clinic with bone deformities. Radiographs of knees and wrists confirmed the presence of florid rickets. The family (including 2 unaffected siblings and the mother) were investigated for hereditary rickets. The three affected siblings had biochemical features of hereditary hypophosphataemic rickets with hypercalciuria (HHRH) with normal plasma calcium and 25-hydroxyvitamin D concentrations, elevated 1,25-dihydroxyvitamin D, hypophosphataemia, hyperphosphaturia and hypercalciuria. At presentation, two of the three affected siblings had an elevated fibroblast growth factor-23 (FGF23) concentration. The mother and clinically unaffected siblings had largely normal biochemistry. Genetic analysis of the SLC34A3 gene, encoding the type IIc sodium-phosphate cotransporter, in DNA samples from the siblings and their mother was conducted. Three single nucleotide polymorphisms (SNPs) S168F, E513V and L599L were identified. E513V and L599L had been previously identified as benign polymorphisms. S168F however, is a previously unreported variant. In silico mutation evaluation predicted that the S168F mutation causes changes in the protein product which are damaging to its function. In addition, the three clinically affected siblings were homozygous in the S168F variant whereas the unaffected family members were carriers. This study describes a biochemical profile and complementary gene data consistent with a rare genetic hypophosphataemic rickets disease in a family from rural Gambia. To our knowledge, this study reports the first cases of HHRH in Africa and describes a novel causal mutation within the SLC34A3 gene. ► A Gambian family of 5 children where 3 siblings had florid rickets with suspected HHRH ► Biochemical profile of hypophosphataemia with elevated urinary phosphate and calcium excretion. ► Genetic analysis of the SLC34A3 gene indicated a novel mutation of S168F. ► The siblings with rickets were homozygous in S168F, the unaffected siblings were carriers. ► We report the first cases of hereditary hypophosphataemic rickets with hypercalciuria in Africa.
登录
查看更多内容
影响因子：
4.1
作者：
Braithwaite, Vickie;Jarjou, Landing M. A.;Prentice, Ann
通讯作者：
Prentice, Ann
影响因子：
4.1
作者：
Prentice, Ann;Ceesay, Mustapha;Pettifor, John M.
通讯作者：
Pettifor, John M.
DOI：
10.1073/pnas.1110905108
发表时间：
2011-11-15
影响因子：
11.1
作者：
Farrow, Emily G.;Yu, Xijie;White, Kenneth E.
通讯作者：
White, Kenneth E.
影响因子：
2
作者：
Thacher, TD;Fischer, PR;Reading, JC
通讯作者：
Reading, JC
影响因子：
9.8
作者：
Bergwitz, C;Roslin, NM;Jüppner, H
通讯作者：
Jüppner, H