2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-A novel <em>de novo</em> microdeletion at 9q33.3, including <em>LHX2</em>, in a patient with developmental delay and autism spectrum disorder

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Researchers at Mayo Clinic have reported a novel microdeletion in a 31-month-old patient with developmental delay and autism spectrum disorder. The microdeletion involves two genes, DENND1A and LHX2, located on chromosome 9 at position 9q33.3. While the pathogenicity of this deletion is still uncertain, the fact that it occurred de novo suggests it may contribute to the patient's clinical presentation.<br /><br />LHX2 is a gene involved in brain development regulation and is thought to be haploinsufficient, meaning that a loss of one copy may lead to developmental abnormalities. It is preferentially expressed in the central nervous system and has been implicated in cortical and hippocampal development. Studies in mice have shown that loss of LHX2 leads to abnormal central nervous system development and lethality.<br /><br />The patient presented with speech delay, global developmental delay, and regression in gross motor skills, social and language skills, and fine motor skills. They also had hyperkinesis and physical features such as a broad forehead, long eyelashes, and mild prognathism. The microdeletion detected on a chromosomal microarray involved a deletion of 599 kb at 9q33.3, encompassing both DENND1A and LHX2.<br /><br />Further research is needed to determine the exact mechanisms by which this microdeletion may cause the observed phenotypic features. Currently, the microdeletion is classified as a variant of unknown significance. However, it is worth noting that there is no overlap with established haploinsufficient genes, no similar microdeletions in the literature, and no disease-causing variants reported for DENND1A or LHX2.<br /><br />Overall, this study highlights a potential role for LHX2 in neurodevelopmental disorders and the importance of chromosomal microarray analysis in the diagnostic evaluation of patients with intellectual disabilities and developmental delays.

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Presenting Author - Marie-France Gagnon, MD, MSc; Co-Author - Sarah Barnett, S., MS, CGC; Co-Author - Subhadra Ramanathan, MS, MSGC; Co-Author - Robin D. Clark, MD; Co-Author - Nicole L. Hoppman, PhD;

Meta Tag

Clinical Cytogenetics

Cognitive Disorders

Cytogenetics

Genetic Testing

Microarray

Co-Author Sarah Barnett, S., MS, CGC

Co-Author Subhadra Ramanathan, MS, MSGC

Co-Author Robin D. Clark, MD

Co-Author Nicole L. Hoppman, PhD

Presenting Author Marie-France Gagnon, MD, MSc

Keywords

Mayo Clinic

microdeletion

developmental delay

autism spectrum disorder

DENND1A

LHX2

chromosome 9

haploinsufficient

central nervous system

neurodevelopmental disorders