Tahir Sophia, Demirbilek Hüseyin, Ozbek Mehmet Nuri, Baran Riza Taner, Tanriverdi Sibel, Hussain Khalid
Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme, UCL Institute of Child Health, Great Ormond Street Hospital for Children, London, UK.
Horm Res Paediatr. 2016;85(5):309-17. doi: 10.1159/000444483. Epub 2016 Mar 17.
Vitamin D-dependent rickets type I (VDDR1) is an autosomal recessive disorder caused by mutations in the 25-hydroxyvitamin D 1-alpha-hydroxylase gene (CYP27B1). Mutations in CYP27B1 disrupt or lead to a total loss of the 1-α-hydroxylase activity and require treatment with physiological doses of calcitriol.
A genetic analysis of the CYP27B1 gene was conducted in 22 Turkish patients with VDDR1 from 13 families. Presenting characteristics, biochemical features, treatment, and results from the genetic analysis are described.
A splice donor site mutation c.195 + 2T>G was found in 10 patients. The novel missense p.192K>E (c.574A>G) mutation was detected in 5 patients, and a novel missense p.197G>D (c.590G>A) mutation was found in 4 patients. A previously reported 7-bp duplication 1319-1325dupCCCACCC (Phe443Profs*24) in exon 8 was detected in 1 patient, and 1 patient was a compound heterozygote for the novel p.192K>E and the previously described 1319-1325dupCCCACCC mutations. A novel single base pair deletion, c.171_171delG, leading to a frameshift, was found in 1 patient.
We identified 3 novel and 2 previously described mutations in the CYP27B1 gene. A marked phenotypical diversity was observed between families that carried identical mutations, suggesting phenotypical heterogeneity.
I型维生素D依赖性佝偻病（VDDR1）是一种常染色体隐性疾病，由25-羟维生素D 1-α-羟化酶基因（CYP27B1）突变引起。CYP27B1突变会破坏1-α-羟化酶活性或导致其完全丧失，需要用生理剂量的骨化三醇进行治疗。
对来自13个家庭的22名患有VDDR1的土耳其患者进行了CYP27B1基因的遗传分析。描述了患者的临床表现、生化特征、治疗情况以及遗传分析结果。
在10名患者中发现了剪接供体位点突变c.195 + 2T>G。在5名患者中检测到新的错义突变p.192K>E（c.574A>G），在4名患者中发现了新的错义突变p.197G>D（c.590G>A）。在1名患者中检测到先前报道的外显子8中的7个碱基对重复1319-1325dupCCCACCC（Phe443Profs*24），1名患者是新的p.192K>E突变与先前描述的1319-1325dupCCCACCC突变的复合杂合子。在1名患者中发现了一个导致移码的新单碱基对缺失c.171_171delG。
我们在CYP27B1基因中鉴定出3个新突变和2个先前描述的突变。在携带相同突变的家庭之间观察到明显的表型多样性，提示表型异质性。
