Objectives Hereditary Hypophosphatemic Rickets (HHR) is a heterogeneous group of disorders characterized by hypophosphatemia. Although the X-linked dominant HHR is the most common form, the genetic etiology of HHR is variable. Recently, developed next-generation sequencing techniques may provide opportunities for making HHR diagnosis in a timely and efficient way. Methods We investigated clinical and genetic features for 18 consecutive probands and their 17 affected family members with HHR. All patient’s clinical and biochemical data were collected. We first analyzed a single gene with Next-generation sequencing if the patients have a strong clue for an individual gene. For the remaining cases, a Hypophosphatemic Rickets gene panel, including all known HHR genes by Next-generation sequencing, was employed. Results We were able to diagnosis all of the consecutive 35 patients in our tertiary care center. We detected nine novel and 10 previously described variants in PHEX (9; 50%), SLC34A3 (3; 17%), ENPP1 (3; 17%), SLC34A1 (1; 5%), CLCN5 (1; 5%), and DMP1 (1; 5%). Conclusions To delineate the etiology of HHR cases in a cost and time-efficient manner, we propose single gene analysis by next-generation sequencing if findings of patients indicate a strong clue for an individual gene. If that analysis is negative or for all other cases, a Next-generation Sequence gene panel, which includes all known HHR genes, should be employed.

中文翻译：

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靶向二代测序在遗传性低磷佝偻病诊断中的经验

目的 遗传性低磷佝偻病 (HHR) 是一组以低磷血症为特征的异质性疾病。尽管 X 连锁显性 HHR 是最常见的形式，但 HHR 的遗传病因是可变的。最近，开发的下一代测序技术可能为及时有效地进行 HHR 诊断提供机会。方法 我们调查了 18 名连续先证者及其 17 名 HHR 受影响家庭成员的临床和遗传特征。收集所有患者的临床和生化数据。如果患者对单个基因有很强的线索，我们首先使用下一代测序分析单个基因。对于其余病例，采用了低磷佝偻病基因组，包括通过下一代测序的所有已知 HHR 基因。结果 我们能够诊断出我们三级医疗中心的所有连续 35 名患者。我们在 PHEX (9; 50%)、SLC34A3 (3; 17%)、ENPP1 (3; 17%)、SLC34A1 (1; 5%)、CLCN5 (1; 5%)、和 DMP1 (1; 5%)。结论 为了以成本和时间高效的方式描述 HHR 病例的病因，如果患者的发现表明单个基因的有力线索，我们建议通过下一代测序进行单基因分析。如果该分析为阴性或所有其他情况，则应使用包含所有已知 HHR 基因的下一代序列基因面板。结论 为了以成本和时间高效的方式描述 HHR 病例的病因，如果患者的发现表明单个基因的有力线索，我们建议通过下一代测序进行单基因分析。如果该分析为阴性或所有其他情况，则应使用包含所有已知 HHR 基因的下一代序列基因面板。结论 为了以成本和时间高效的方式描述 HHR 病例的病因，如果患者的发现表明单个基因的有力线索，我们建议通过下一代测序进行单基因分析。如果该分析为阴性或所有其他情况，则应使用包含所有已知 HHR 基因的下一代序列基因面板。