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| Skeletal dysplasia v2.184 | LRRK1 |
Eleanor Williams Tag Q3_21_rating was removed from gene: LRRK1. Tag Q3_21_NHS_review was removed from gene: LRRK1. |
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| Skeletal dysplasia v2.184 | LRRK1 | Eleanor Williams commented on gene: LRRK1: The rating of this gene has been updated following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.183 | LRRK1 |
Eleanor Williams Source Expert Review Green was added to LRRK1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Skeletal dysplasia v2.128 | LRRK1 | Eleanor Williams Classified gene: LRRK1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.128 | LRRK1 | Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber, but with a recommendation for a green rating following GMS review. More than 3 reported cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.128 | LRRK1 | Eleanor Williams Gene: lrrk1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.127 | LRRK1 |
Eleanor Williams Tag Q3_21_rating tag was added to gene: LRRK1. Tag Q3_21_NHS_review tag was added to gene: LRRK1. |
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| Skeletal dysplasia v2.127 | LRRK1 | Eleanor Williams commented on gene: LRRK1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.127 | LRRK1 | Eleanor Williams Phenotypes for gene: LRRK1 were changed from Osteosclerotic metaphyseal dysplasia (OSMD) (OMIM: 615198) to Osteosclerotic metaphyseal dysplasia (OSMD), OMIM: 615198; Osteosclerotic metaphyseal dysplasia, MONDO:0014080 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.119 | LRRK1 |
Conor Pallatt gene: LRRK1 was added gene: LRRK1 was added to Skeletal dysplasia. Sources: NHS GMS,Literature Mode of inheritance for gene: LRRK1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRK1 were set to 27829680; 27055475; 31571209; 32119750 Phenotypes for gene: LRRK1 were set to Osteosclerotic metaphyseal dysplasia (OSMD) (OMIM: 615198) Penetrance for gene: LRRK1 were set to Complete Review for gene: LRRK1 was set to GREEN Added comment: A detailed phenotypic picture of Osteosclerotic metaphyseal dysplasia (OSMD) in patients with LRRK1 variants can be seen in table 1 of Howaldt et al (2020). Lida et al (2016) identified homozygous deletion that is predicted to result in elongation of protein (p.E1980Afs*66) in a child with OSMD. Child was born to consanguineous parents, both heterozygous for variant. Guo et al (2017) identified a family with OSMD. Healthy, non-consanguineous parents have two children with OSMD that are homozygous for 1bp insertion in LRRK1 that is predicted to result in a frame-shift and produce an elongated protein (p.A1991Gfs*31) without nonsense-mediated mRNA decay. A similar effect seen in Lida et al (2016). Howaldt et al (2020) shows a patient with a homozygous splice site mutation resulting in near complete skipping of exon 3 in cDNA leading to a frameshift (p.Ala34Profs*33). The variant segregated with disorder in the family with parents being heterozygous for the variant and clinically unaffected. Miryounesi et al (2020) identified a patient with suspected OSMD from healthy, consanguineous parents. Patient is homozygous for stop gain mutation (c.2785G > T, p.E929X) in LRRK1. Parents are heterozygous for the variant. Homozygous nonsense variant in LRRK1 also identified in an individual recruited to the 100,000 genomes project for skeletal dysplasia, Osteosclerotic metaphyseal dysplasia is considered a good fit for phenotype. LRRK1 gene should be included in the skeletal dysplasia panel as a green gene at the next GMS panel update. Sources: NHS GMS, Literature |
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