RecruitingNCT05062629

United States Hypophosphatasia Molecular Research Center

Sponsor

Children's Mercy Hospital Kansas City

Enrollment

66 participants

Start Date

Aug 24, 2021

Study Type

OBSERVATIONAL

Conditions

Hypophosphatasia

Summary

This study is being done to determine if cryptic alterations exist within or near to the ALPL gene in patients with a clinical diagnosis of hypophosphatasia, but without identifiable alteration on commercial testing. Additionally, the study aims to characterize functional effects of certain variants of uncertain significance in patients with clinical diagnosis of hypophosphatasia.

Eligibility

Inclusion Criteria10

Aim 1-
Diagnosis of Hypophosphatasia based on clinical features that include
History consistent with diagnosis of hypophosphatasia AND
Physical examination findings consistent with a diagnosis of hypophosphatasia AND
Presence of low serum alkaline phosphatase level for age and sex AND
Elevation of at least one natural substrate of alkaline phosphatase
Lack of detection of a variant on molecular analysis of the ALPL gene. When possible, first degree relatives (parents, siblings, or child) will be included for the sole purpose of trio testing. No additional information will be collected on first degree relatives.
Aim 2-
Missense variant in ALPL which is interpreted as a variant of uncertain significance by the American College of Medical Genetics Guidelines for Variant Interpretation
Variant has been interpreted as pathogenic, likely pathogenic, likely benign, or benign using ex-US interpretation guidelines

Exclusion Criteria7

Aim 1-
History and physical examination incompatible with a diagnosis of hypophosphatasia OR
Absence of hypophosphatasemia as measured by age and sex-matched control OR
Absence of at least one elevated natural substrate of alkaline phosphatase OR
Alternate diagnosis which could overlap with signs and symptoms of hypophosphatasia
Aim 2-
\. Inability to express variant in plasmid for residual enzyme and co-transfection analyses