Novel variants and uncommon cases among southern Chinese children with X-linked hypophosphatemia
- PDF / 1,841,546 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 13 Downloads / 174 Views
ORIGINAL ARTICLE
Novel variants and uncommon cases among southern Chinese children with X‑linked hypophosphatemia 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. Zeng1 · L. Liu1 Received: 6 February 2020 / Accepted: 24 March 2020 © Italian Society of Endocrinology (SIE) 2020
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. Keywords X-linked hypophosphatemia · PHEX gene · Southern China · Mutational spectrum · Clinical features
Introduction Hypophosphatemia is a group of rare genetic diseases that occur as a consequence of chaotic phosphate metabolism and defective bone mineralization with a manifestation of hypophosphatemia, skeletal malformations, growth retardation and short stature. According to the causative gene and inheritance pattern, hypophosphatemia is categorized as X-linked hypophosphatemia (XLH), autosomal dominant Yunting Lin and Jianan Xu contributed equally to this work. * C. Zeng [email protected] * L. Liu [email protected] 1
Department of Genetics and Endocrinology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Rd., Guangzhou 510623, China
hypophosphatemia (ADH), autosomal recessive hypophosphatemia (ARH), hereditary hypophosphatemic rickets with hypercalciuria (HHRH) and tumor-induced osteomalacia (TIO) [1, 2]. Among the hereditary hypophosphatemia as well as inherited rickets, XLH (OMIM # 307800) is the most common form accounting for over 80% of familial cases and about 70% of sporadic cases, with an estimated prevalence of 1/20,000–60,000 [3–11]. Generally, XLH patients fail to thrive and present lower extremity deformities, osteoporosis, bone pain and poor skeletal and de
Data Loading...
