Identification of Rare and Novel PHEX Variants in X-linked Hypophosphatemia.

Autor:	Ma X; Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China., Pang Q; Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China., Gong Y; Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China., Li X; Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China., Liu W; Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China., Jiang Y; Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China., Wang O; Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China., Li M; Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China., Xing X; Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China., Xia W; Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Nov 18; Vol. 109 (12), pp. 3176-3185.
DOI:	10.1210/clinem/dgae299
Abstrakt:	Context: X-linked hypophosphatemia (XLH) is a rare metabolic bone disease caused by inactivation mutations in the PHEX gene. Despite the extensive number of reported PHEX variants, only a few cases of chromosomal abnormalities have been documented. Objective: We aimed to identify the pathogenic variants in 6 unrelated families with a clinical diagnosis of XLH and to propose a genetic workflow for hypophosphatemia patients suspected of having XLH. Methods: Multiple genetic testing assays were used to analyze the 6 families' genetic profiles, including whole exome sequencing, multiplex ligation-dependent probe amplification, whole genome sequencing, reverse transcript polymerase chain reaction, Sanger sequencing, and karyotyping. Results: The study identified 6 novel pathogenic variants, including 1 mosaic variant (exon 16-22 deletion), 3 chromosomal abnormalities (46, XN, inv[X][pter→p22.11::q21.31→p22.11::q21.31 →qter], 46, XN, inv[X][p22.11p22.11], and XXY), a nonclassical intron variant (NM_000444.6, c.1701_31A > G), and a deletion variant (NM_000444.6, c.64_5464-186 del5215) of PHEX. Additionally, a genetic testing workflow was proposed to aid in diagnosing patients suspected of XLH. Conclusion: Our research expands the mutation spectrum of PHEX and highlights the significance of using multiple genetic testing methods to diagnose XLH. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
Databáze:	MEDLINE
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