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| Severe microcephaly v3.5 | PRIM1 | Arina Puzriakova Tag Q2_21_rating was removed from gene: PRIM1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v3.5 | PRIM1 | Arina Puzriakova commented on gene: PRIM1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v3.4 | PRIM1 |
Arina Puzriakova 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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| Severe microcephaly v2.322 | PRIM1 | Eleanor Williams commented on gene: PRIM1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.322 | 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.321 | PRIM1 | Eleanor Williams Tag gene-checked was removed from gene: PRIM1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.300 | PRIM1 | Arina Puzriakova Tag gene-checked tag was added to gene: PRIM1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.111 | PRIM1 | Arina Puzriakova edited their review of gene: PRIM1: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.111 | PRIM1 | Arina Puzriakova Classified gene: PRIM1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.111 | PRIM1 | Arina Puzriakova Added comment: Comment on list classification: 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.111 | PRIM1 | Arina Puzriakova Gene: prim1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v2.110 | PRIM1 |
Arina Puzriakova Tag watchlist was removed from gene: PRIM1. Tag Q2_21_rating tag was added to gene: PRIM1. |
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| Severe microcephaly v2.105 | PRIM1 |
Arina Puzriakova gene: PRIM1 was added gene: PRIM1 was added to Severe microcephaly. Sources: Literature watchlist 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 AMBER 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 |
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