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| Skeletal dysplasia v10.8 | HPGD | Ida Ertmanska changed review comment from: Comment on mode of inheritance: Out of more than 70 Primary hypertrophic osteoarthropathy (PHO) patients reported in literature, only 3 of them habroured monoallelic HPGD variants and were reported to have a mild phenotype. Some het carrier family members in recessive pedigrees presented with mild digital clubbing. Based on available evidence, the heterozygous cases are not in scope of the Skeletal dysplasia panel, and the mode of inheritance should be changed to BIALLELIC only.; to: Comment on mode of inheritance: Out of more than 70 Primary hypertrophic osteoarthropathy (PHO) patients reported in literature, only 3 of them habroured monoallelic HPGD variants and only direct HPGD/SLCO2A1 Sanger sequencing was used in these studies. Some het carrier family members in recessive pedigrees presented with mild digital clubbing - not in scope of this panel. Based on available literature, the evidence for a dominant association is limited and the mode of inheritance should be changed to BIALLELIC only. An expert_review tag was added to ensure GMS agreement regarding this change. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v10.8 | HPGD |
Ida Ertmanska changed review comment from: PMID: 35813463 Lu et al., 2022 Study of 12 Chinese Primary hypertrophic osteoarthropathy (PHO) patients from 11 families. Direct HPGD sequencing revealed 7 different mutations. The recurrent mutation c.310_311delCT were found in all eleven patients. 11/12 individuals had biallelic HPGD mutations. The heterozygous patient P1 habroured the c.310_311delCT variant and had a mild phenotype (mild finger clubbing, periostosis, and mild pachydermia). Digital clubbing and periostosis were the most common shared features, with pachydermia, hyperhidrosis, and joint swelling also frequently reported. The study's literature reviews states that only 2/77 PHO patients reported in literature had monoallelic HPGD variants. PMID: 26135126 Yuan et al., 2015 Study of 2 sibs and 7 sporadic cases with primary hypertrophic osteoarthropathy. A recurrent c.310_311delCT mutation was identified in all patients, of which six were homozygous, two were heterozygous, and one was compound heterozygous with this mutation and a novel heterozygous missense mutation c.488G>A (p.R163H). Seq method: Sanger seq of HPGD only. Heterozygous individuals (P8 and P9) were het for the c.310_311del variant. Both individuals had digital clubbing. P8 also showed pachydermia, while P9 presented with periostosis, joint swelling, and hyperhidrosis. The authors acknowledge the possiblity that a second undetectable null mutation may have been missed in the het patients, due to limitations of Sanger sequencing. Variant HPGD:c.310_311del, p.Leu104Alafs*3 has MAF = 0.0004281 (East Asian pop), with no hmz reported in gnomAD v4. PMID: 18500342 Uppal et al., 2008 Report of 4 families with PHO, probands harboured biallelic HPGD variants. Some heterozygous family members were also noted to have mild digital clubbing. 2/4 families are from North Pakistan, both probands were homozygous for p.Ala140Pro and confirmed to be distantly related on haplotype analysis. The affected individuals in other 2 families, 1 described as Polish and non-consanguineous, harboured homozygous putative LoF variants. Only HPGD was sequenced, using PCR amplification. HPGD is only associated with recessive disease entities in OMIM (Cranioosteoarthropathy, Hypertrophic osteoarthropathy, primary, autosomal recessive 1, ?Digital clubbing, isolated congenital) and G2P (HPGD-related cranioosteoarthropathy, biallelic_autosomal) - resources accessed 10th Sept 2026.; to: PMID: 35813463 Lu et al., 2022 Study of 12 Chinese Primary hypertrophic osteoarthropathy (PHO) patients from 11 families. Direct HPGD sequencing revealed 7 different mutations. The recurrent mutation c.310_311delCT were found in all eleven patients. 11/12 individuals had biallelic HPGD mutations. All patients were negative for SLCO2A1 mutations. The heterozygous patient P1 habroured the c.310_311delCT variant and had a mild phenotype (mild finger clubbing, periostosis, and mild pachydermia). Digital clubbing and periostosis were the most common shared features, with pachydermia, hyperhidrosis, and joint swelling also frequently reported. The study's literature reviews states that only 2/77 PHO patients reported in literature had monoallelic HPGD variants. PMID: 26135126 Yuan et al., 2015 Study of 2 sibs and 7 sporadic cases with primary hypertrophic osteoarthropathy. A recurrent c.310_311delCT mutation was identified in all patients, of which six were homozygous, two were heterozygous, and one was compound heterozygous with this mutation and a novel heterozygous missense mutation c.488G>A (p.R163H). Seq method: Sanger seq of HPGD only. Heterozygous individuals (P8 and P9) were het for the c.310_311del variant. Both individuals had digital clubbing. P8 also showed pachydermia, while P9 presented with periostosis, joint swelling, and hyperhidrosis. The authors acknowledge the possiblity that a second undetectable null mutation may have been missed in the het patients, due to limitations of Sanger sequencing. They were negative for SLCO2A1 mutations. Variant HPGD:c.310_311del, p.Leu104Alafs*3 has MAF = 0.0004281 (East Asian pop), with no hmz reported in gnomAD v4. PMID: 18500342 Uppal et al., 2008 Report of 4 families with PHO, probands harboured biallelic HPGD variants. Some heterozygous family members were also noted to have mild digital clubbing. 2/4 families are from North Pakistan, both probands were homozygous for p.Ala140Pro and confirmed to be distantly related on haplotype analysis. The affected individuals in other 2 families, 1 described as Polish and non-consanguineous, harboured homozygous putative LoF variants. Only HPGD was sequenced, using PCR amplification. HPGD is only associated with recessive disease entities in OMIM (Cranioosteoarthropathy, Hypertrophic osteoarthropathy, primary, autosomal recessive 1, ?Digital clubbing, isolated congenital) and G2P (HPGD-related cranioosteoarthropathy, biallelic_autosomal) - resources accessed 10th Sept 2026. |
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| Skeletal dysplasia v8.37 | SLCO2A1 | Eleanor Williams Tag Q2_25_ MOI was removed from gene: SLCO2A1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v8.37 | SLCO2A1 | Eleanor Williams commented on gene: SLCO2A1: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v8.36 | SLCO2A1 | Eleanor Williams Mode of inheritance for gene SLCO2A1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v8.4 | SLCO2A1 | Sarah Leigh Tag Q2_25_ MOI tag was added to gene: SLCO2A1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v8.4 | SLCO2A1 | Sarah Leigh edited their review of gene: SLCO2A1: Added comment: SLCO2A1 variants are associated with autosomal recessive and autosomal dominant forms of primary hypertrophic osteoarthropathy (OMIM:614441, OMIM:167100) in numerous cases (PMID:23509104; 27134495; 33852188; 22331663; 27134495).; Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v8.4 | SLCO2A1 | Sarah Leigh Publications for gene: SLCO2A1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v8.3 | SLCO2A1 | Sarah Leigh Phenotypes for gene: SLCO2A1 were changed from Hypertrophic osteoarthropathy, primary, autosomal recessive 2 614441; Hypertrophic osteoarthropathy, primary, autosomal recessive 2 614441 to Hypertrophic osteoarthropathy, primary, autosomal recessive 2 OMIM:614441; hypertrophic osteoarthropathy, primary, autosomal recessive, 2, MONDO:0013756; Hypertrophic osteoarthropathy, primary, autosomal dominant, OMIM:167100; hypertrophic osteoarthropathy, primary, autosomal dominant, MONDO:0008172 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v7.5 | SLCO2A1 | Dmitrijs Rots reviewed gene: SLCO2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.105 | SLCO2A1 | Zornitza Stark reviewed gene: SLCO2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23509104, 27134495, 33852188, 22331663, 27134495; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100, Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.153 | SLCO2A1 | Eleanor Williams Added phenotypes Hypertrophic osteoarthropathy, primary, autosomal recessive 2 614441 for gene: SLCO2A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.147 | SLCO2A1 | Tracy Lester reviewed gene: SLCO2A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal recessive 2 614441; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.146 | SLCO2A1 | Eleanor Williams reviewed gene: SLCO2A1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.145 | SLCO2A1 |
Eleanor Williams Source NHS GMS was added to SLCO2A1. Rating Changed from Green List (high evidence) to Green List (high evidence) |
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