United States Hypophosphatasia Molecular Research Center

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.

CT.gov Identifier
NCT05062629
EudraCT Identifier
N/A
CTIS:
N/A
Sponsor
Children's Mercy Hospital Kansas City
Collaborator
N/A
Study Contact Information
N/A
Recruiting
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Study Details

Diseases
Hypophosphatasia
Study Drug
Whole genome sequencing
Genes
ALPL
Study Dates
Aug 2021 - Mar 2026
Sex
Female & Male
Age
N/A
Inclusion and Exclusion Criteria
Inclusion Criteria:
  • Aim 1-
  • 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
  • 2. 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-
  • 1. Missense variant in ALPL which is interpreted as a variant of uncertain significance by the American College of Medical Genetics Guidelines for Variant Interpretation
  • 2. Variant has been interpreted as pathogenic, likely pathogenic, likely benign, or benign using ex-US interpretation guidelines
Exclusion Criteria:
  • Aim 1-
  • 1. History and physical examination incompatible with a diagnosis of hypophosphatasia OR
  • 2. Absence of hypophosphatasemia as measured by age and sex-matched control OR
  • 3. Absence of at least one elevated natural substrate of alkaline phosphatase OR
  • 4. Alternate diagnosis which could overlap with signs and symptoms of hypophosphatasia
  • Aim 2-
  • 1. Inability to express variant in plasmid for residual enzyme and co-transfection analyses

Protocol 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.

Study Locations

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