United States Hypophosphatasia Molecular Research Center

Launched by CHILDREN'S MERCY HOSPITAL KANSAS CITY · Sep 21, 2021

Keywords

ClinConnect Summary

The United States Hypophosphatasia Molecular Research Center is conducting a clinical trial to learn more about a condition called hypophosphatasia, which affects the bones and teeth. This study is looking for patients who have been diagnosed with hypophosphatasia but whose genetic tests did not show any clear changes in a specific gene called ALPL. The researchers want to see if there are hidden genetic changes near this gene that could help explain the condition. They will also examine certain genetic variations that are not clearly understood to see how they might affect patients with hypophosphatasia.

To participate in this study, you need to be diagnosed with hypophosphatasia based on specific symptoms and lab results, including low levels of a certain enzyme in your blood. You must not have any identifiable changes in the ALPL gene from previous tests. The study is open to individuals aged 30 and above, and it welcomes all genders. If you qualify and decide to join, you'll contribute to important research that could improve understanding and treatment of hypophosphatasia. Additionally, if you have close family members who also have this condition, they may be included for testing purposes, although no additional information will be collected from them.

Gender

ALL

Eligibility 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