Y Lin1, J Xu1, X Li1, H Sheng1, L Su1, M Wu1, J Cheng1, Y Huang1, X Mao1, Z Zhou1, W Zhang1, C Li1, Y Cai1, D Wu1, Z Lu1, X Yin1, C Zeng2, L Liu3. 1. Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Rd., Guangzhou, 510623, China. 2. Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Rd., Guangzhou, 510623, China. chunhuazeng@hotmail.com. 3. Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Rd., Guangzhou, 510623, China. liliuchina@qq.com.
Abstract
PURPOSE: X-linked hypophosphatemia (XLH) is the most common inherited renal phosphate wasting disorder and is often misdiagnosed as vitamin D deficiency. This study aims to provide clinical and mutational characteristics of 65 XLH pediatric patients in southern China. METHODS: In this work, a combination of DNA sequencing and qPCR analysis was used to study the PHEX gene in 80 pediatric patients diagnosed with hypophosphatemia. The clinical and laboratory data of confirmed 65 XLH patients were assessed and analyzed retrospectively. RESULTS: In 65 XLH patients from 61 families, 51 different variants in the PHEX gene were identified, including 23 previously reported variants and 28 novel variants. In this cohort of XLH patients, the c.1601C>T(p.Pro534Leu) variant appears more frequently. Fourteen uncommon XLH cases were described, including four boys with de novo mosaic variants, eight patients with large deletions and a pair of monozygotic twins. The clinical manifestations in this cohort are very similar to those previously reported. CONCLUSION: This study extends the mutational spectrum of the PHEX gene, which will contribute to accurate diagnosis. This study also suggests a supplementary qPCR or MLPA assay may be performed along with classical sequencing to confirm the gross insertion/deletion.
PURPOSE:X-linked hypophosphatemia (XLH) is the most common inherited renal phosphate wasting disorder and is often misdiagnosed as vitamin D deficiency. This study aims to provide clinical and mutational characteristics of 65 XLH pediatric patients in southern China. METHODS: In this work, a combination of DNA sequencing and qPCR analysis was used to study the PHEX gene in 80 pediatric patients diagnosed with hypophosphatemia. The clinical and laboratory data of confirmed 65 XLHpatients were assessed and analyzed retrospectively. RESULTS: In 65 XLHpatients from 61 families, 51 different variants in the PHEX gene were identified, including 23 previously reported variants and 28 novel variants. In this cohort of XLHpatients, the c.1601C>T(p.Pro534Leu) variant appears more frequently. Fourteen uncommon XLH cases were described, including four boys with de novo mosaic variants, eight patients with large deletions and a pair of monozygotic twins. The clinical manifestations in this cohort are very similar to those previously reported. CONCLUSION: This study extends the mutational spectrum of the PHEX gene, which will contribute to accurate diagnosis. This study also suggests a supplementary qPCR or MLPA assay may be performed along with classical sequencing to confirm the gross insertion/deletion.
Authors: Michaël R Laurent; Jean De Schepper; Dominique Trouet; Nathalie Godefroid; Emese Boros; Claudine Heinrichs; Bert Bravenboer; Brigitte Velkeniers; Johan Lammens; Pol Harvengt; Etienne Cavalier; Jean-François Kaux; Jacques Lombet; Kathleen De Waele; Charlotte Verroken; Koenraad van Hoeck; Geert R Mortier; Elena Levtchenko; Johan Vande Walle Journal: Front Endocrinol (Lausanne) Date: 2021-03-19 Impact factor: 5.555