Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: ATAD3A

Comment on list classification: New gene added to this panel by Boaz Palterer (University of Florence). Although the Lepelley et al. 2021 (PMID: 34387651) paper described multiple patients with interferon signalling disturbances it does not appear likely that this would form the basis for diagnostic testing in a clinical setting. ATAD3A is associated with a wide spectrum of clinical features but immune phenotypes do not appear particularly prominent. However, as two patients in PMID: 34387651 did demonstrate signs consistent with standardised criteria for a diagnosis of the autoimmune disorder systemic sclerosis, rating Amber for now awaiting further evidence supporting inclusion on this panel.

Created: 18 Apr 2023, 10:48 a.m. | Last Modified: 18 Apr 2023, 10:48 a.m.

Panel Version: 4.4

Green List (high evidence)

Leppeley et al. described 8 patients across 7 kindreds (one inherited and 7 de novo), with mono or biallelic variants in ATAD3A. Patients presented with a wide clinical spectrum and all presented elevated IFN signature.
Functional data provided: "Knockdown of ATAD3A in THP-1 cells resulted in increased interferon signaling, mediated by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Enhanced interferon signaling was abrogated in THP-1 cells and patient fibroblasts depleted of mtDNA."
Sources: Literature

Created: 6 Jul 2022, 12:49 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Developmental delay; Hypotonia; Dystonia; Systemic sclerosis; Autoimmunity; Contractures; Basal ganglia calcifications; Interferonopathy

Publications

• 34387651