Severe microcephalyGene: ATRIP
In a patient, born of consanguineous Gujarati-Indian parents, with Seckel syndrome (OMIM:210600), Ogi et al. (PMID:23144622, 2012) identified a heterozygous c.2278C-T transition in exon 12 of the ATRIP gene, resulting in an arg760-to-ter (R760X) substitution. The unaffected mother also carried the mutation. The paternal allele carried a splicing defect affecting exon 2 that was likely subject to NMD. The patient had severe microcephaly (-10 SD), micrognathia, dental crowding, small earlobes, delayed bone age, and symmetric dwarfism. The clinical and cellular phenotype was similar to that observed in Seckel patients with ATR mutations but the link between the variant and Seckel syndrome has not been established.
Created: 13 Dec 2016, 10:43 a.m.
2nd March 2017: Panel review was assessed and panel was revised according to expert review and additional curation. This panel began with an expert gene list from Professor Andrew Jackson (University of Edinburgh) for primary microcephaly (MCPH) and microcephalic primordial dwarfism (MPD). Other disorders are included where microcephaly is a primary feature. Disorders where microcephaly is not the primary presenting feature are not included (e.g. congenital disorders of glycosylation, Proud syndrome, Norrie disease). The panel does not include disorders with a cortical malformation (e.g. lissencephaly) since the Malformations of cortical development' panel would be applied to these patients.
This gene has been classified as Red List (Low Evidence).
ATRIP was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Source: Other
ATRIP was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Expert list
ATRIP was created by rfoulger