Paediatric disorders - additional genes

Gene: ATRIP

Green List (high evidence)

Comment on list classification: There are now 3 unrelated probands reported in literature with severe microcephaly consistent with Seckel syndrome, habrouring homozygous variants in ATRIP. Other syndromic features have been reported, including immunodeficiency, short stature, and developmental delay. Hence, ATRIP can be promoted to Green on this panel.

Created: 27 Oct 2026, 11:52 a.m. | Last Modified: 27 Oct 2026, 11:52 a.m.

Panel Version: 8.21

PMID: 40029331 Duthoo et al., 2025
Study identified homozygous splice ATRIP variants in two patients of independent ancestry with microcephaly, primordial dwarfism, and recurrent infections.
Patient F1Pt: female with severe microcephaly, developmental delay, dysmorphic features, growth retardation (final height of 133 cm at age 22 yrs), grossly normal skeletal development (skeletal radiography revealed osteoporotic changes in the bones, delayed bone age, and the presence of 11 pairs of ribs, without other unusual skeletal developmental issues), and a mild ID. She had recurrent respiratory tract infections. Lab investigations showed lymphopenia and intermittent neutropenia. WES revealed a homozygous c.829+5G>T variant in ATRIP. Based on figure S1, severity of microcephaly was close to -6 SD below mean for OFC.
Second patient, F46.1, was previously reported in PMID: 35568357.

PMID: 35568357 Masih et al., 2022
Report of 87 Indian families with microcephaly.
P F46.1 - 5yo male - presented with microcephaly OFC 38cm (Z score − 9.4), moderate ID/DD, febrile seizures, facial dysmorphism, dry skin, recurrent respiratory tract infections, clubbing of digits, short stature, speech delay. CT was normal. He was diagnosed with Seckel syndrome. Proband harboured a homozygous ATRIP variant: c.829+2T>G. Method: exome seq.

PMID: 23144622 Ogi et al., 2012
Report of a patient, born of consanguineous Gujarati-Indian parents, with Seckel syndrome. Proband harboured comp het ATRIP variants: c.2278C-T, p.Arg760Ter and a splicing defect c.248-14A<G. Parents confirmed het for a variant each and unaffected. The patient had severe microcephaly (-10 SD), micrognathia, dental crowding, small earlobes, delayed bone age, and symmetric dwarfism.
Reappraisal of patient CV1720’s clinical status in PMID: 40029331 revealed a phenotype of late-onset lymphopenia and intermittent neutropenia.

ATRIP is not yet associated with a disease entity in OMIM. ClinGen and G2P only list AD associations with breast cancer susceptibility. Resources accessed 27th Oct 2026.

Created: 27 Oct 2026, 11:46 a.m. | Last Modified: 27 Oct 2026, 11:53 a.m.

Panel Version: 8.21

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Seckel syndrome, MONDO:0019342; Recurrent infections, HP:0002719

Publications

• 23144622
• 35568357
• 40029331