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. 2025 Apr 2:1-5.
doi: 10.1159/000545445. Online ahead of print.

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

Cheryl Weiqi Tan  1 , Jiin Ying Lim  2 , Khadijah Rafi'ee  1 , Jeannette Goh  2   3 , Chew Thye Choong  3   4 , Sing Ming Chao  3   5 , Benjamin Chang  6 , Saumya S Jamuar  2   3 , Ene-Choo Tan  1   3
Affiliations

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

Cheryl Weiqi Tan et al. Mol Syndromol. .

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Camptodactyly; GATAD2B-associated neurodevelopmental disorder; Macrocephaly; Nucleosome remodelling and deacetylase complex.

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Conflict of interest statement

All authors declare no conflicts of interest.

Figures

Fig. 1.
Fig. 1.
a Front and side profiles of the patient at age 7 showing macrocephaly, flattened nasal bridge, and frontal bossing. Dissociated vertical deviation could also be seen. b Top (left image) and side (right image) views of the camptodactyly observed in the right 5th finger. c Cranial MRI at 5 years of age showing ventriculomegaly.
Fig. 2.
Fig. 2.
Chromatogram from Sanger sequencing showing the deletion of the C nucleotide in the child. The variant is not present in her parents’ samples.
See this image and copyright information in PMC

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