Andary Rabih, El-Hage-Sleiman Abdul-Karim, Farhat Theresa, Sanjad Sami, Nemer Georges
Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut.
Department of Pediatrics and Adolescent Medicine, American University of Beirut, Bliss Street, Beirut.
J Pediatr Endocrinol Metab. 2017 Apr 1;30(4):437-444. doi: 10.1515/jpem-2016-0338.
Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder caused by mutations in the vitamin D receptor (VDR) gene. Variable phenotypes have been associated with these mutations, and some of these were linked to the effects they have on the interacting partners of VDR, mainly the retinoic X receptor (RXR).
We examined four patients with HVDRR from three unrelated Lebanese families. All parents were consanguineous with normal phenotype. We used Sanger sequencing to identify mutations in the coding exons of VDR.
Two homozygous mutations (p.R391S and p.H397P), both in exon 9 of the VDR gene, were identified. Phenotype/genotype association was not possible even for the same mutation. Alopecia was seen only with the p.R391S mutation. Despite a comparable rachitic bone disease, the patients showed different responsiveness to large doses of alfacalcidol (1-α-hydroxy vitamin D3) supplementation.
This is the first report of VDR mutations in Lebanon with promising clinical outcomes despite the severity of the phenotypes.
遗传性维生素D抵抗性佝偻病（HVDRR）是一种常染色体隐性疾病，由维生素D受体（VDR）基因突变引起。这些突变与多种不同的表型相关，其中一些与它们对VDR相互作用伴侣（主要是维甲酸X受体（RXR））的影响有关。
我们研究了来自三个不相关黎巴嫩家庭的四名HVDRR患者。所有父母均为近亲结婚且表型正常。我们使用桑格测序法来鉴定VDR编码外显子中的突变。
在VDR基因的第9外显子中鉴定出两个纯合突变（p.R391S和p.H397P）。即使对于相同的突变，也无法确定表型/基因型之间的关联。仅在p.R391S突变中观察到脱发。尽管患有类似的佝偻病性骨病，但患者对大剂量阿法骨化醇（1-α-羟基维生素D3）补充剂的反应不同。
这是黎巴嫩关于VDR突变的首次报告，尽管表型严重，但临床结果良好。
