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Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 | PRIM1 | Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: PRIM1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Primary immunodeficiency or monogenic inflammatory bowel disease v3.4 | PRIM1 | Achchuthan Shanmugasundram reviewed gene: PRIM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Primary immunodeficiency or monogenic inflammatory bowel disease v3.3 | PRIM1 |
Achchuthan Shanmugasundram Source Expert Review Green was added to PRIM1. Source NHS GMS was added to PRIM1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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Primary immunodeficiency or monogenic inflammatory bowel disease v2.582 | PRIM1 | Eleanor Williams commented on gene: PRIM1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Primary immunodeficiency or monogenic inflammatory bowel disease v2.582 | PRIM1 | Eleanor Williams Phenotypes for gene: PRIM1 were changed from Microcephalic primordial dwarfism, MONDO:0017950 to Microcephalic primordial dwarfism, MONDO:0017950; Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, OMIM:620005 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Primary immunodeficiency or monogenic inflammatory bowel disease v2.581 | PRIM1 | Eleanor Williams Tag gene-checked was removed from gene: PRIM1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Primary immunodeficiency or monogenic inflammatory bowel disease v2.548 | PRIM1 | Arina Puzriakova Tag gene-checked tag was added to gene: PRIM1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Primary immunodeficiency or monogenic inflammatory bowel disease v2.413 | PRIM1 | Arina Puzriakova Classified gene: PRIM1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Primary immunodeficiency or monogenic inflammatory bowel disease v2.413 | PRIM1 | Arina Puzriakova Added comment: 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Primary immunodeficiency or monogenic inflammatory bowel disease v2.413 | PRIM1 | Arina Puzriakova Gene: prim1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Primary immunodeficiency or monogenic inflammatory bowel disease v2.412 | PRIM1 |
Arina Puzriakova 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 Added comment: 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. Sources: Literature |