A Novel GATAD2B Frameshift Variant Causes GATAD2B-Associated Neurodevelopmental Disorder with Camptodactyly

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Molecular Biology

Background:

• GATAD2B-associated neurodevelopmental disorder (GAND) results from pathogenic variants in the GATAD2B gene.
• Key features include intellectual disability, speech impairment, and dysmorphism, which are non-specific and require molecular confirmation.
• Diagnosis is challenging due to overlapping symptoms with other neurodevelopmental syndromes.

Purpose of the Study:

• To report the first case of GAND in a patient of Southeast Asian (Korean-Chinese) heritage.
• To characterize the genetic and phenotypic spectrum of GAND.
• To highlight the utility of advanced genetic testing in diagnosing rare neurodevelopmental disorders.

Main Methods:

• Clinical evaluation including prenatal and postnatal assessments (MRI).
• Standard genetic testing: chromosomal microarray, targeted gene panel, exome sequencing.
• Variant confirmation: Sanger sequencing for de novo status.

Main Results:

• A de novo heterozygous single nucleotide deletion (p.His216Metfs*24) in the GATAD2B gene was identified via exome sequencing.
• Initial investigations including chromosomal microarray and targeted gene panels were normal.
• Sanger sequencing confirmed the variant was de novo.

Conclusions:

• The identification of a novel de novo GATAD2B variant expands the genotypic spectrum of GAND.
• This case broadens the phenotypic description of GAND in a previously underrepresented demographic.
• Genetic testing, particularly exome sequencing, is crucial for definitive diagnosis of GAND.