Data_Sheet_1_Genotype and Phenotype Analysis in X-Linked Hypophosphatemia.docx

Background: X-linked hypophosphatemia (XLH) is the most frequent form of hypophosphatemic rickets and is caused by mutations in the PHEX gene. We analyzed genotype-phenotype correlations in XLH patients with proven PHEX mutations.
Methods:PHEX mutations were detected in 55 out of 81 patients who clinically presented with hypophosphatemic rickets. The patients were grouped into nontruncating (n = 9) and truncating (n = 46) mutation groups; their initial presentation as well as long-term clinical findings were evaluated according to these groups.
Results: Initial findings, including presenting symptoms, onset age, height standard deviation scores (SDS), and laboratory tests, including serum phosphate level and tubular resorption of phosphate, were not significantly different between the two groups (onset age: nontruncating mutation group, 2.0 years, truncating mutation group, 2.2 years; height SDS: nontruncating mutation group, −1.9, truncating mutation group, −1.7; serum phosphate: nontruncating mutation group, 2.5 mg/dL, truncating mutation group, 2.6 mg/dL). However, at their last follow-up, the serum phosphate level was significantly lower in patients with truncating mutations (nontruncating mutation group: 3.2 mg/dl, truncating mutation group: 2.3 mg/dl; P = 0.006). Additionally, 62.5% of patients with truncating mutations developed nephrocalcinosis at their last follow-up, while none of the patients with nontruncating mutations developed nephrocalcinosis (P = 0.015). Orthopedic surgery due to bony deformations was performed significantly more often in patients with truncating mutations (52.3 vs. 10.0%, P = 0.019).
Conclusion: Although considerable inconsistency exists regarding the correlation of truncating mutations and their disease phenotype in several other studies, we cautiously suggest that there would be genotype-phenotype correlation in some aspects of disease manifestation after long-term follow-up. This information can be used when consulting patients with confirmed XLH regarding their disease prognosis.

研究背景：X连锁低磷血症（X-linked hypophosphatemia, XLH）是低磷性佝偻病最常见的类型，由PHEX基因发生突变引发。本研究针对经证实携带PHEX突变的XLH患者，分析其基因型与表型的相关性。
研究方法：在81例临床诊断为低磷性佝偻病的患者中，共检出55例携带PHEX突变。将该55例患者分为非截短突变组（n=9）与截短突变组（n=46），并依据分组对患者的初始临床表现及长期临床结局进行评估。
研究结果：两组患者的初始表现（包括首发症状、发病年龄、身高标准差评分（height standard deviation scores, SDS））以及实验室检查指标（包括血清磷水平、肾小管磷重吸收率）均无显著差异（发病年龄：非截短突变组2.0岁，截短突变组2.2岁；身高SDS：非截短突变组-1.9，截短突变组-1.7；血清磷：非截短突变组2.5 mg/dL，截短突变组2.6 mg/dL）。但在末次随访时，截短突变组患者的血清磷水平显著低于非截短突变组（非截短突变组3.2 mg/dL，截短突变组2.3 mg/dL；P=0.006）。此外，截短突变组中有62.5%的患者在末次随访时出现肾钙化症，而非截短突变组无1例发生肾钙化症（P=0.015）。截短突变组因骨畸形接受骨科手术的比例显著高于非截短突变组（52.3% vs 10.0%，P=0.019）。
研究结论：尽管既往多项研究中关于截短突变与疾病表型的相关性存在较大分歧，但本研究谨慎提出，在长期随访的疾病表现层面，XLH存在一定的基因型-表型相关性。该研究结果可为确诊XLH患者的疾病预后咨询提供参考依据。