2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-An Analysis of <em>ALPL </em>Gene Variants in Patients With Hypophosphatasia From the Global Hypophosphatasia Registry

Pdf Summary

This study analyzed the ALPL gene variants in patients with hypophosphatasia (HPP) enrolled in the Global HPP Registry. HPP is a rare metabolic disorder characterized by low alkaline phosphatase activity due to ALPL gene variants. The study aimed to describe the ALPL variants in a large cohort of HPP patients. <br /><br />Most patients in the study had pediatric-onset HPP and were white and female. The majority of patients had at least one non-benign variant, with the exception of Japan where a higher proportion of patients had two or more non-benign variants. Variants were classified based on their pathogenicity, and the most common variant effect was missense. However, in Japan, a higher proportion of frameshift variants were identified. <br /><br />The study also identified 28 patients with unique and novel variants, including variants such as c.1018C>T and c.1327G>T. The study provides insights into the distribution of ALPL variants in HPP patients from different geographic regions.<br /><br />Overall, this analysis of the Global HPP Registry data showed that most patients had identified ALPL variants. The variant status, pathogenicity, and effects were similar across geographic regions, except for more variants and frameshift variants in Japan. The study helps improve the understanding of the genetic basis of HPP and can aid in the diagnostic process for patients with this rare disease.

Asset Subtitle

Co-Author - Priya Kishnani, MD; Co-Author - Kathryn M. Dahir, MD; Co-Author - Gabriel Á. Martos-Moreno, MD, PhD; Co-Author - Agnès Linglart, MD, PhD; Co-Author - Anna Petryk, MD; Presenting Author - William R. Mowrey, PhD; Co-Author - Shona Fang, ScD; Co-Author - Cheryl Rockman-Greenberg, MD, CM; Co-Author - Keiichi Ozono, MD; Co-Author - Wolfgang Högler, MD; Co-Author - Lothar Seefried, MD;

Meta Tag

Biochemical genetics

Epigenetics

Genotype-Phenotype Correlations

Identification of Disease Genes

Population Genetics

Co-Author Priya Kishnani, MD

Co-Author Kathryn M. Dahir, MD

Co-Author Gabriel Á. Martos-Moreno, MD, PhD

Co-Author Agnès Linglart, MD, PhD

Co-Author Anna Petryk, MD

Co-Author Shona Fang, ScD

Co-Author Cheryl Rockman-Greenberg, MD, CM

Co-Author Keiichi Ozono, MD

Co-Author Wolfgang Högler, MD

Co-Author Lothar Seefried, MD

Presenting Author William R. Mowrey, PhD

Keywords

ALPL gene variants

hypophosphatasia

Global HPP Registry

metabolic disorder

alkaline phosphatase activity

pediatric-onset HPP

pathogenicity

missense variants

frameshift variants

unique and novel variants