Primary immunodeficiencyGene: PRIM1
Comment on list classification: PRIM1 was added to this panel following discussion with Helen Brittain (Genomics England Clinical Team). It was agreed that there is sufficient evidence to rate this gene Green at the next review
Created: 12 Apr 2021, 4:03 p.m. | Last Modified: 12 Apr 2021, 4:03 p.m.
Panel Version: 2.413
PRIM1 is currently not associated with any phenotype in OMIM (last edited in 2004) or Gene2Phenotype.
- PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).
Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.
Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Created: 12 Apr 2021, 4:02 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Microcephalic primordial dwarfism, MONDO:0017950
Gene: prim1 has been classified as Amber List (Moderate Evidence).
gene: PRIM1 was added gene: PRIM1 was added to Primary immunodeficiency. Sources: Literature Q2_21_rating tags were added to gene: PRIM1. Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRIM1 were set to 33060134 Phenotypes for gene: PRIM1 were set to Microcephalic primordial dwarfism, MONDO:0017950 Review for gene: PRIM1 was set to GREEN