2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Mosaic Variant in <em>RHOA</em> in an Adolescent with a Multisystem Disorder Composed of Congenital and Progressive Anomalies

Mosaic Variant in RHOA in an Adolescent with a Multisystem Disorder Composed of Congenital and Progressive Anomalies

Pdf Summary

This case study describes a 14-year-old female patient with a multisystem disorder characterized by a combination of congenital and progressive anomalies. The patient presented with a history of large bowel obstruction, hemiatrophy (asymmetric wasting of the face, chest wall, and extremities), scalp cutis aplasia, skin hypopigmentation, brachydactyly (short fingers), oligodontia (missing teeth), sensorineural deafness, leukoencephalopathy (white matter brain abnormalities), and ophthalmologic disease. She had previously been diagnosed with autism spectrum disorder.<br /><br />Genetic testing was performed on DNA extracted from cultured fibroblasts from the patient's forearms. The analysis revealed a pathogenic variant in the RHOA gene, specifically the c.139G>A (p.Glu47Lys) variant. This variant was found in 44% of the alleles in the fibroblasts from the right forearm, but not in those from the left forearm. Additional genetic testing using blood-derived DNA did not identify this variant.<br /><br />The RHOA gene is responsible for encoding a GTPase that plays a role in various cellular processes, including cell adhesion, migration, and proliferation. Mutations in this gene have been associated with a condition called RHOA-related mosaic neuroectodermal dysplasia. This condition is characterized by features such as hypopigmentation, facial asymmetry, acral anomalies, dental and ocular anomalies, and abnormal brain MRI findings. The patient in this case study exhibited many of these features.<br /><br />The authors emphasize that RHOA-related mosaic neuroectodermal dysplasia should be considered in individuals with pigmentary abnormalities, progressive body asymmetry, and congenital anomalies such as colonic atresias, dental anomalies, and ocular anomalies. They also highlight the importance of early detection and diagnosis for monitoring patients for progressive vision and hearing impairment.<br /><br />Further research and characterization of this disorder are needed to better understand its outcomes and natural history. The authors suggest that there may be other undiagnosed individuals with this condition who could benefit from confirmatory testing using fibroblast-extracted DNA sequencing of the RHOA gene.

Asset Subtitle

Presenting Author - Aimee Allworth, MS, LCGC; Co-Author - Ian A. Glass, MBChB, MD, FACMG; Co-Author - Anne Hing, MD; Co-Author - Elizabeth Blue, PhD; Co-Author - Elisabeth A. Rosenthal, PhD; Co-Author - Sam Strohbehn, BS; Co-Author - Gail P. Jarvik, MD, PhD; Co-Author - Katrina M. Dipple, MD, PhD; Co-Author - Andrew B. Stergachis, M.D., Ph.D; Co-Author - Virginia P. Sybert, MD; Co-Author - Jane Ranchalis, BS; Co-Author - Martha Horike-Pyne, MPH; Co-Author - Sirisak Chanprasert, MD; Co-Author - Fuki M. Hisama, MD, FACMG, FAAN; Co-Author - Michael J. Bamshad, MD; Co-Author - James T. Bennett, MD, PhD; Co-Author - Heather A. Brandling-Bennett, MD; Co-Author - Michelle T. Cabrera, MD; Co-Author - Mark H. Wener, MD;

Meta Tag

Variant Detection

Sequencing

Phenotypic delineation of disorders

Phenotype

Malformation

Identification of Disease Genes

Genomic Methodologies

Genetic Testing

Gastrointestinal System

Eye disorders

Exome sequencing

Etiology

Delineation of Diseases

Congenital Anomaly

Clinical History

Brain/Nervous System

Auditory System

Co-Author Katrina M. Dipple, MD, PhD

Co-Author Andrew B. Stergachis, M.D., Ph.D

Co-Author Virginia P. Sybert, MD

Co-Author Jane Ranchalis, BS

Co-Author Martha Horike-Pyne, MPH

Co-Author Sirisak Chanprasert, MD

Co-Author Fuki M. Hisama, MD, FACMG, FAAN

Co-Author Michael J. Bamshad, MD

Co-Author James T. Bennett, MD, PhD

Co-Author Heather A. Brandling-Bennett, MD

Co-Author Michelle T. Cabrera, MD

Co-Author Mark H. Wener, MD

Co-Author Gail P. Jarvik, MD, PhD

Co-Author Sam Strohbehn, BS

Co-Author Elisabeth A. Rosenthal, PhD

Co-Author Elizabeth Blue, PhD

Co-Author Anne Hing, MD

Co-Author Ian A. Glass, MBChB, MD, FACMG

Presenting Author Aimee Allworth, MS, LCGC

Keywords

multisystem disorder

congenital anomalies

large bowel obstruction

hemiatrophy

RHOA gene

pathogenic variant

GTPase

RHOA-related mosaic neuroectodermal dysplasia

dental anomalies

ocular anomalies