Vitamin D-dependent rickets type IA (VDDR-IA) is caused by biallelic mutations in CYP27B1. Data regarding genotype–phenotype correlation in VDDR-IA are scarce. Here, we aimed to investigate clinical/genotypic features and long-term follow-up of 13 new cases with VDDR-IA and genotype–phenotype correlation of reported cases in the literature. Thirteen patients with VDDR-IA were evaluated. Eight patients had reached their final height at the time of the study and, for whom, long-term outcome data were analyzed. Further, all VDDR-IA patients in the literature (n:183) were analyzed and clinical–genetic features were recorded. The median age of diagnosis was 2.55 ± 1.13 (1.0–12) years. Initial diagnoses before referral to our clinic were nutritional rickets (n:7), hypophosphatemic rickets (n:2), and pseudohypoparathyroidism (n:1). All had biochemical evidence suggestive of VDDR-IA; except one with elevated 1,25(OH)₂D3 and another with hyperphosphatemia, in whom pseudohypoparathyroidism was excluded with molecular tests. Combined analyses of our cohort and other series in the literature demonstrated that three most common CYP27B1 mutations are p.F443Pfs*24, c.195 + 2T > G, and p.V88Wfs*71. In Turkish population, p.K192E mutation along with the former two is the most common mutations. Comparison of clinical features demonstrated that c.195 + 2T > G mutation causes the most severe and p.K192E mutation causes the least severe phenotype with respect to age and height at presentation and calcitriol requirement. We found a clear genotype–phenotype correlation in VDDR-IA, notably CYP27B1 intronic c.195 + 2T > G mutation causes a more severe phenotype with lower height SDS at presentation and, higher calcitriol requirement, while less severe phenotype occurs in p.K192E mutation.

维生素 D 依赖性佝偻病 IA 型 (VDDR-IA) 是由CYP27B1的双等位基因突变引起的. 关于 VDDR-IA 中基因型-表型相关性的数据很少。在这里，我们旨在调查 13 例 VDDR-IA 新病例的临床/基因型特征和长期随访以及文献中报告病例的基因型 - 表型相关性。评估了 13 名 VDDR-IA 患者。八名患者在研究时达到了他们的最终身高，并对他们的长期结果数据进行了分析。此外，对文献中的所有 VDDR-IA 患者 (n:183) 进行了分析，并记录了临床遗传特征。诊断的中位年龄为 2.55 ± 1.13 (1.0-12) 岁。转诊到我们诊所之前的初步诊断是营养性佝偻病（n:7）、低磷性佝偻病（n:2）和假性甲状旁腺功能减退症（n:1）。所有人都有提示 VDDR-IA 的生化证据；_{1,25(OH) 2}升高的除外D3 和​​另一个患有高磷血症，通过分子检测排除了假性甲状旁腺功能减退症。对我们的队列和文献中其他系列的综合分析表明，三种最常见的CYP27B1突变是 p.F443Pfs*24、c.195 + 2T > G 和 p.V88Wfs*71。在土耳其人群中，p.K192E 突变与前两者一起是最常见的突变。临床特征的比较表明，c.195 + 2T > G 突变导致最严重的表型，而 p.K192E 突变导致最不严重的表型，就出现时的年龄和身高以及骨化三醇的需求而言。我们在 VDDR-IA 中发现了明确的基因型-表型相关性，尤其是CYP27B1内含子 c.195 + 2T > G 突变导致更严重的表型，呈现时具有较低的高度 SDS 和较高的骨化三醇需求，而在 p.K192E 突变中出现较不严重的表型。