2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Broadening the Phenotype of ABL1-Associated Disorder

Pdf Summary

This study discusses the ABL1 gene and its association with chronic myeloid leukemia, as well as the newly discovered germline pathogenic variants in the ABL1 gene that result in various features such as joint contractures, poor growth, dysmorphic facial features, congenital heart disease, microcephaly, and developmental delays. The study reports a new patient with ABL1-associated disorder caused by a specific variant and presents features not previously described, including thumb duplication, double outlet right ventricle with subaortic ventricular septal defect, and anterior chamber anomalies.<br /><br />The patient in the case presentation was born prematurely and showed physical characteristics such as micrognathia, microcephaly, microphthalmia, elongated nose, hypoplastic alae, and overlapping digits with clenched fists. They also had a heart abnormality, specifically a double outlet right ventricle with a subaortic ventricular septal defect. Other examinations, such as renal and brain ultrasounds, were normal. Genetic testing revealed a pathogenic variant in the ABL1 gene.<br /><br />The study suggests that these findings might expand the phenotype of ABL1-associated disorder. There are overlapping features with intrauterine growth restriction, microcephaly, camptodactyly, narrow nose, and hypoplastic alae, although ear anomalies were not present in this patient. The study emphasizes the importance of identifying and reporting additional patients with this disorder in order to gain a better understanding of its medical issues. The concentration of pathogenic variants in the functional kinase domain of the ABL1 gene suggests that further research is needed to investigate the mechanisms of the disease and genotype-phenotype relationships.<br /><br />In summary, this study reports a patient with ABL1-associated disorder caused by a specific variant and describes features not previously associated with the disorder. The study underscores the need for further research and the reporting of additional cases to better understand the spectrum of medical issues associated with this rare disorder.

Asset Subtitle

Co-Author - Christopher Vincent, MD; Presenting Author - Daniel Groepper, LGC; Co-Author - Lamya Mubayed, MD; Co-Author - Julie Fleischer, MD;

Meta Tag

Bone/Joint Abnormalities

Cardiac/circulatory disorders

Cardiovascular System

Congenital Anomaly

Delineation of Diseases

Dysmorphology

Etiology

Eye disorders

Gene Localization

Genotype-Phenotype Correlations

Malformation

Musculoskeletal system

Phenotype

Phenotypic delineation of disorders

Co-Author Christopher Vincent, MD

Co-Author Lamya Mubayed, MD

Co-Author Julie Fleischer, MD

Presenting Author Daniel Groepper, LGC

Keywords

ABL1 gene

chronic myeloid leukemia

germline pathogenic variants

congenital heart disease

microcephaly

thumb duplication

double outlet right ventricle

subaortic ventricular septal defect

pathogenic variant

ABL1-associated disorder