2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-XLH Molecular Diagnoses and the <em>PHEX </em>Gene<em> </em>Variant Landscape: Sponsored Hypophosphatemia Gene Panel Testing Findings from 2019 versus 2022

XLH Molecular Diagnoses and the PHEX Gene Variant Landscape: Sponsored Hypophosphatemia Gene Panel Testing Findings from 2019 versus 2022

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This document is a summary of a study on XLH, a rare genetic disorder that affects males and females of all ages. XLH is caused by a specific gene variant in the PHEX gene, which leads to elevated serum FGF23 and below-normal serum phosphate levels. The disorder is characterized by various clinical symptoms including rickets, osteomalacia, short stature, lower limb deformities, muscle pain, bone pain, and hearing difficulty, among others.<br /><br />The study focused on the use of a sponsored gene panel for the diagnosis of XLH and other genetic hypophosphatemia. The study found that there was a 3.7-fold increase in unique PHEX variants since 2019, with 514 unique variants observed as of October 2022. The distribution of variant subtypes remained similar over time. The study also found a decrease in the number of variants of uncertain significance (VUS) from 11% in 2019 to 6% in 2022.<br /><br />Cascade testing and the resolution of VUS have been valuable in aiding the molecular diagnosis of XLH. The study observed an increase in the use of the program by a broader range of clinical specialties over time. The top three specialties utilizing the program in 2019 were endocrinology, genetics, and nephrology, while in 2022, endocrinology, family medicine, and genetics were the top three followed by nephrology and rheumatology.<br /><br />Overall, the study highlights the importance of genetic testing and the use of gene panels in the diagnosis of XLH and other genetic disorders. It also emphasizes the need for ongoing research and increased awareness of XLH and its clinical manifestations.

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Presenting Author - Nicole Miller, PhD; Co-Author - Omid K. Japalaghi, MS; Co-Author - Eric T. Rush, MD; Co-Author - Kathryn M. Dahir, MD; Co-Author - Prameela Ramesan, MD; Co-Author - Heather McLaughlin, PhD, FACMG;

Meta Tag

Bone/Joint Abnormalities

Genetic Testing

X-Inactivation/X-Linked Disease

Co-Author Omid K. Japalaghi, MS

Co-Author Eric T. Rush, MD

Co-Author Kathryn M. Dahir, MD

Co-Author Prameela Ramesan, MD

Co-Author Heather McLaughlin, PhD, FACMG

Presenting Author Nicole Miller, PhD

Keywords

XLH

genetic disorder

PHEX gene

FGF23

rickets

osteomalacia

short stature

gene panel

diagnosis

genetic testing