ClinGen Dosage Sensitivity Curation Page

GATAD2B

  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
23644463 Three patients (Patient 1, 2 and 4) with a heterozygous mutation resulting in the loss-of-function of GATAD2B. The overlapping abnormal phenotype were severe intellectual disability, limited speech, childhood hypotonia, strabismus, long fingers, thin hair and recognizable facial features, which include a typical, tubular shaped nose with broad tip, deeply set eyes, broad forehead, short philtrum, broad mouth, grimacing facial expression. Patient 1 had a de novo nonsense mutation (c.1408C>T or p.(Gln470*)) located in the conserved region 2 (CR2) domain of the GATAD2B gene. Patient 2 had a de novo frameshift mutation (c.584dup or p.(Asn195Lysfs*30)) located at the conserved region 1 (CR1). Patient 4 had a 2-bp deletion near the CR1 domain resulting in a frameshift mutation (c.565_566del or p.(Gln190Alafs*34)). The mother of patient 4 is a healthy mosaic carrier (<10% in peripheral blood) of the same mutation. Studies in Drosophila model demonstrated that reduced levels of GATAD2B orthologue (simj-RNAi flies) affect learning and synapse development.
28077840 Two patients with a de novo heterozygous mutation resulting in the loss-of-function of GATAD2B gene. The overlapping abnormal phenotype include intellectual disability, language delay, palpebral fissue, ocular hypertelorism, and a flat, low nasal bridge. Individual 1 had a 5-bp insertion upstream from CR1 domain resulting in a frameshift and premature termination (c.80_81insGATGT or p.(Leu28Metfs*18)). Individual 2 had 4-bp deletion within the CR1 domain resulting in a frameshift and premature termination (c.552_555delGAAA or p.(Lys184Asnfs*2)).
27848944 One patient (00080965) with a de novo heterozygous mutation resulting in the loss-of-function of GATAD2B gene. The clinical features include global developmental delay, delayed speech and language development, motor delay, morphological abnormality of the central nervous system, congenital encephalopathy, strabismus, hyperreflexia, muscular hypotonia of trunk, seizures and others. The mutation resulting in a frameshift and premature termination (c.815_816insTCCA or p.(Gln272Hisfs*11)).

Haploinsufficiency phenotype comments:

Other reports with a de novo mutation resulting in the loss-of-function of GATAD2B gene include PMID: 25356899 (Patient 1907.666) and 27159321 (Patient LD_0366). In addition, large de novo heterozygous deletions at 1q21.3, including GATAD2B gene, had been reported with variable breakpoints and sizes (145-1,095kb) in the following papers PMID: 23644463 (Patient 3) and 28211977. Despite many other genes involved in the large deletion at 1q21.3, these patients shared some similar features to those being described above with a small DNA sequence mutation of GATAD2B gene.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity