Shanghai Clinical Research Center of Bone Diseases, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Front Endocrinol (Lausanne). 2022 Aug 19;13:956646. doi: 10.3389/fendo.2022.956646. eCollection 2022.
The aim of this study was to fully describe the clinical and genetic characteristics, including clinical manifestations, intact fibroblast growth factor 23 (iFGF23) levels, and presence of gene mutations, of 22 and 7 patients with familial and sporadic X-linked dominant hypophosphatemia (XLH), respectively.
Demographic data, clinical features, biochemical indicators, and imaging data of 29 patients were collected. All 22 exons and exon-intron boundaries of the gene were amplified by polymerase chain reaction (PCR) and directly sequenced. The serum level of iFGF23 was measured in 15 of the patients.
Twenty-nine patients (male/female: 13:16, juvenile/adult: 15:14) with XLH were included. The main symptoms were bowed lower extremities (89.7%), abnormal gait (89.7%), and short stature/growth retardation (78.6%). Hypophosphatemia with a high alkaline phosphatase level was the main biochemical feature and the median value of serum iFGF23 was 55.7 pg/ml (reference range: 16.1-42.2 pg/ml). Eight novel mutations in the gene were identified by Sanger sequencing, including two missense mutations (p. Gln682Leu and p. Phe312Ser), two deletions (c.350_356del and c.755_761del), one insertion (c.1985_1986insTGAC), and three splice mutations (c.1700+5G>C, c.1966-1G>T, and c.350-14_350-1del). Additionally, the recurrence rate after the first orthopedic surgery was 77.8% (7/9), and five of them had their first surgery before puberty.
Our study expanded the clinical phenotypes and gene mutation spectrum of XLH and provided a reference for the optimal timing of orthopedic surgeries.
本研究旨在全面描述 22 例家族性和 7 例散发性 X 连锁显性低磷血症（XLH）患者的临床和遗传特征，包括临床表现、完整成纤维细胞生长因子 23（iFGF23）水平和基因突变情况。
收集 29 例患者的人口统计学资料、临床特征、生化指标和影像学资料。应用聚合酶链反应（PCR）扩增 基因的 22 个外显子和外显子-内含子边界，并直接测序。对 15 例患者进行血清 iFGF23 水平测定。
共纳入 29 例（男/女：13/16，青少年/成人：15/14）XLH 患者。主要症状为下肢弯曲（89.7%）、步态异常（89.7%）和身材矮小/生长迟缓（78.6%）。低磷血症伴碱性磷酸酶水平升高为主要生化特征，血清 iFGF23 中位数为 55.7pg/ml（参考范围：16.1-42.2pg/ml）。通过 Sanger 测序鉴定出 基因的 8 个新突变，包括 2 个错义突变（p.Gln682Leu 和 p.Phe312Ser）、2 个缺失突变（c.350_356del 和 c.755_761del）、1 个插入突变（c.1985_1986insTGAC）和 3 个剪接突变（c.1700+5G>C、c.1966-1G>T 和 c.350-14_350-1del）。此外，首次矫形手术后的复发率为 77.8%（7/9），其中 5 例在青春期前进行了首次手术。
本研究扩展了 XLH 的临床表型和基因突变谱，为矫形手术的最佳时机提供了参考。
