Novel PHEX gene locus-specific database: Comprehensive characterization of vast number of variants associated with X-linked hypophosphatemia (XLH)

Hum Mutat. 2022 Feb;43(2):143-157. doi: 10.1002/humu.24296.

PMID: 34806794

Soodabeh Sarafrazi, Sean C Daugherty, Nicole Miller

Highlights: To centralize and disseminate PHEX variant information, a new PHEX gene locus-specific database, PHEX LSDB, has been established.

Abstract

Background: The most prevalent type of hereditary hypophosphatemia, X-linked hypophosphatemia (XLH), is brought on by disrupting variants in the PHEX gene, which is located on the X chromosome. Both males and females exhibit 100% penetrance of the X-linked pattern of inheritance for XLH. Chronic hypophosphatemia causes lifetime symptoms for patients, such as poor bone mineralization, skeletal abnormalities, growth retardation, and decreased quality of life. Chronic conditions need to be managed throughout the rest of one's life with disease-specific treatments, which can enhance patient outcomes, especially when started at a young age.

Objective: A brand-new PHEX gene locus-specific database have been developed, called PHEX LSDB, to organize and distribute PHEX variant data. The PHEX LSDB has 870 distinct PHEX variants as of April 30, 2021, which were gathered from an earlier database of PHEX variants, extensive literature research, a sponsored genetic testing program, and XLH clinical trials. This information is made available to the public on a searchable, interactive website (https://www.rarediseasegenes.com/), which also has an online form for reporting new PHEX variants and a table of variants and related information. New variants reported via the website, found in the published literature, or shared from genetic testing programs will be added to the database on a regular basis.

Keywords: PHEX, X-linked hypophosphatemia (XLH), locus-specific database, osteomalacia, rickets