Objectives Vitamin D dependent rickets type 1A (VDDR-1A) is a very rare autosomal recessive disorder caused by mutations in the CYP27B1 , which encodes vitamin D 1α-hydroxylase. We report the genetics and clinical manifestations of nine patients with VDDR-1A and compare our patients to other cases with the same mutations in the literature. Methods The clinical presentations, clinical and laboratory findings and treatment modalities of the patients were evaluated retrospectively. Results The mean age of the patients at the time of diagnosis was 39.9 months (range: 4.5–111). At the time of diagnosis, six patients had received stoss vitamin D therapy. Clinical findings related to rickets were obvious in seven patients and unclear in two patients. Except for one case, all patients had laboratory findings of rickets. A novel variant and four previously reported mutations in CYP27B1 were identified. The mean calcitriol and elemental calcium dose were 45.5 ng/kg/day (range: 20–70) and 75.6 mg/kg/day (range: 45–125), respectively. Conclusions We found a novel compound heterozygous mutation consisting of a reported duplication [(p.F443Pfs*24 (c.1319_1325 dup CCCACCC)] in exon 8 and a novel deletion [p.D507Efs*34 (c.1521 delC)] in exon 9. Our study suggests that the clinical manifestations and laboratory findings of the patients with VDDR1A are variable even among the patients with the same mutation.

中文翻译：

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1A型维生素D依赖佝偻病患者的遗传学和临床表现

目的 1A 型维生素 D 依赖性佝偻病 (VDDR-1A) 是一种非常罕见的常染色体隐性遗传病，由编码维生素 D 1α-羟化酶的 CYP27B1 突变引起。我们报告了 9 名 VDDR-1A 患者的遗传学和临床表现，并将我们的患者与文献中具有相同突变的其他病例进行了比较。方法回顾性评价患者的临床表现、临床和实验室检查结果以及治疗方法。结果 诊断时患者的平均年龄为 39.9 个月（范围：4.5-111）。在诊断时，有6名患者接受了斯托斯维他命D治疗。与佝偻病相关的临床表现在 7 名患者中明显，在 2 名患者中不清楚。除一例外，所有患者均有佝偻病的实验室检查结果。鉴定了 CYP27B1 中的一个新变体和四个先前报道的突变。平均骨化三醇和元素钙剂量分别为 45.5 ng/kg/天（范围：20–70）和 75.6 mg/kg/天（范围：45–125）。结论 我们发现了一种新的复合杂合突变，由外显子 8 中报告的重复 [(p.F443Pfs*24 (c.1319_1325 dup CCCACCC)] 和外显子中的新缺失 [p.D507Efs*34 (c.1521 delC)] 组成9. 我们的研究表明，即使在具有相同突变的患者中，VDDR1A 患者的临床表现和实验室检查结果也存在差异。