Research on genetic alterations in hypophosphatasia patients
United States Hypophosphatasia Molecular Research Center
This study is trying to find hidden genetic changes in the ALPL gene of people with hypophosphatasia to better understand their condition and how it affects their bones.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 66 (estimated) |
| Ages | 1 Month to 120 Years |
| Sex | All |
| Sponsor | Children's Mercy Hospital Kansas City Academic / other |
| Locations | 1 site (Kansas City, Missouri) |
| Trial ID | NCT05062629 on ClinicalTrials.gov |
What this trial studies
This observational study aims to identify hidden genetic alterations in the ALPL gene among patients diagnosed with hypophosphatasia who do not show identifiable changes on standard genetic tests. It will utilize whole genome sequencing to explore these cryptic alterations and assess the functional effects of certain genetic variants that are currently classified as uncertain. Additionally, the study seeks to enhance the understanding of hypophosphatasemia in patients with skeletal diseases. The research will include both patients with a clinical diagnosis of hypophosphatasia and their first-degree relatives for comprehensive genetic analysis.
Who should consider this trial
Good fit: Ideal candidates include individuals with a clinical diagnosis of hypophosphatasia who have not had identifiable genetic variants detected through commercial testing.
Not a fit: Patients who have already been identified with pathogenic variants in the ALPL gene or those without a clinical diagnosis of hypophosphatasia may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could lead to improved genetic understanding and management of hypophosphatasia, potentially guiding more effective treatments.
How similar studies have performed: While this approach is innovative, similar studies have shown promise in uncovering hidden genetic factors in other conditions, suggesting potential for success.
Eligibility criteria
Show full inclusion / 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
Where this trial is running
Kansas City, Missouri
- Children's Mercy Hospital — Kansas City, Missouri, United States (Recruiting)
Study contacts
- Principal investigator: Eric Rush — Children's Mercy Hospital Kansas City
- Study coordinator: Eric Rush
- Email: hpp@cmh.edu
- Phone: 816-302-3290
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.