ClinGen Dosage Sensitivity Curation Page

GATAD2B

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function 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)).

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.