Department of Endocrinology, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Research Center for Diabetes, Urumqi, 830000, China.
Department of Endocrinology, Yecheng County, Kashi City of Xinjiang Uygur Autonomous Region, Kashi City, 832000, China.
BMC Pediatr. 2024 Feb 14;24(1):121. doi: 10.1186/s12887-024-04589-2.
Hereditary hypophosphatemia rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder characterised by reduced renal phosphate reabsorption leading to hypophosphataemia, rickets and bone pain. Here, we present a case of HHRH in a Chinese boy.
We report a 11-year-old female proband, who was admitted to our hospital with bilateral genuvarum deformity and short stature. Computed Tomography (CT) showed kidney stones, blood tests showed hypophosphatemia, For a clear diagnosis, we employed high-throughput sequencing technology to screen for variants. Our gene sequencing approach encompassed whole exome sequencing, detection of exon and intron junction regions, and examination of a 20 bp region of adjacent introns. Flanking sequences are defined as ±50 bp upstream and downstream of the 5' and 3' ends of the coding region.The raw sequence data were compared to the known gene sequence data in publicly available sequence data bases using Burrows-Wheeler Aligner software (BWA, 0.7.12-r1039), and the pathogenic variant sites were annotated using Annovar. Subsequently, the suspected pathogenic variants were classified according to ACMG's gene variation classification system. Simultaneously, unreported or clinically ambiguous pathogenic variants were predicted and annotated based on population databases. Any suspected pathogenic variants identified through this analysis were then validated using Sanger sequencing technology. At last, the proband and her affected sister carried pathogenic homozygous variant in the geneSLC34A3(exon 13, c.1402C > T; p.R468W). Their parents were both heterozygous carriers of the variant. Genetic testing revealed that the patient has anLRP5(exon 18, c.3917C > T; p.A1306V) variant of Uncertain significance, which is a rare homozygous variant.
This case report aims to raise awareness of the presenting characteristics of HHRH. The paper describes a unique case involving variants in both theSLC34A3andLRP5genes, which are inherited in an autosomal recessive manner. This combination of gene variants has not been previously reported in the literature. It is uncertain whether the presence of these two mutated genes in the same individual will result in more severe clinical symptoms. This report shows that an accurate diagnosis is critical, and with early diagnosis and correct treatment, patients will have a better prognosis.
遗传性低血磷性佝偻病伴高钙尿症（HHRH）是一种罕见的常染色体隐性遗传病，其特征为肾脏磷酸盐重吸收减少导致低血磷症、佝偻病和骨痛。在此，我们报告一例中国男孩的 HHRH 病例。
我们报告了一例 11 岁女性先证者，因双侧膝内翻和身材矮小而入院。计算机断层扫描（CT）显示肾结石，血液检查显示低磷血症。为明确诊断，我们采用高通量测序技术筛选变异。我们的基因测序方法包括全外显子组测序、检测外显子和内含子连接区，以及检查相邻内含子的 20bp 区域。侧翼序列定义为编码区 5'和 3'末端上下游 50bp。使用 Burrows-Wheeler Aligner 软件（BWA，0.7.12-r1039）将原始序列数据与公共可用序列数据库中的已知基因序列数据进行比较，并使用 Annovar 注释致病变异位点。随后，根据 ACMG 的基因变异分类系统对疑似致病变异进行分类。同时，根据人群数据库预测和注释未报告或临床意义不明的致病变异。通过该分析识别的任何疑似致病变异均通过 Sanger 测序技术进行验证。最后，先证者及其受累姐妹均携带基因 SLC34A3（exon 13，c.1402C>T；p.R468W）的纯合致病性变异。其父母均为该变异的杂合携带者。遗传检测显示，患者存在罕见的纯合 LR P5（exon 18，c.3917C>T；p.A1306V）变异，其意义不确定。
本病例报告旨在提高对 HHRH 表现特征的认识。本文描述了一例同时携带 SLC34A3 和 LRP5 基因变异的独特病例，这些变异以常染色体隐性方式遗传。这两种基因变异的组合在文献中尚未报道过。尚不清楚这两种突变基因在同一个体中的存在是否会导致更严重的临床症状。本报告表明准确的诊断至关重要，早期诊断和正确治疗将使患者有更好的预后。
