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

GATAD2B-associated neurodevelopmental disorder (GAND) is caused by pathogenic variants in GATAD2B which encodes p66beta, a subunit of a transcription repressor. The main presentations of GAND are intellectual disability, speech impairment, and dysmorphism. However, these features overlap with other neurodevelopmental syndromes and are not specific enough to be recognised for a particular clinical diagnosis without molecular confirmation.

Macrocephaly was detected prenatally and at birth. Postnatal brain MRI also revealed ventriculomegaly. Chromosomal microarray analysis and metabolites in plasma, serum, or urine were investigated due to microcephaly and dysmorphism, and all results were normal. Next-generation sequencing using a targeted gene panel did not identify any pathogenic variant. Exome sequencing was subsequently performed.

A heterozygous single nucleotide deletion in exon 5 of GATAD2B (p.His216Metfs*24) was detected and Sanger validated. Targeted Sanger sequencing of parental samples showed that it is de novo.

We describe the first patient with GAND from Southeast Asia with Korean-Chinese parentage. The identification of a pathogenic variant in GATAD2B clarifies her diagnosis and adds to the genotypic and phenotypic spectrum of this disorder. This report illustrates the use of genetic testing to obtain a definite diagnosis.