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| Lysosomal storage disorder v1.71 | VPS16 |
Arina Puzriakova gene: VPS16 was added gene: VPS16 was added to Lysosomal storage disorder. Sources: Literature Q2_21_rating, Q2_21_MOI tags were added to gene: VPS16. Mode of inheritance for gene: VPS16 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS16 were set to 33938619; 34013567 Phenotypes for gene: VPS16 were set to Mucopolysaccharidosis-like syndrome (biallelic); Dystonia 30, OMIM:619291; Dystonia Associated with Lysosomal Abnormalities (monoallelic) Review for gene: VPS16 was set to GREEN Added comment: Four individuals from three families were identified (PMIDs: 33938619; 34013567) exhibiting a mucopolysaccharidosis (MPS)-like lysosomal storage phenotype with short stature, coarse facies, DD or regression, peripheral neuropathy, skeletal dysplasia, neutropenia, and high-normal glycosaminoglycan excretion. All harboured homozygous variants in VPS16 which segregated with disease, including a missense variant in a sib pair (c.540G>T; p.Trp180Cys) and a recurrent intronic variant (c.2272‐18C>A) in two supposedly unrelated patients (although both of Middle Eastern descent). Fibroblasts of the two patients with the intronic variant showed accumulation of lysosomal compartments and autophagosomes with significantly decreased VPS16 mRNA and protein levels, as well as HOPS/CORVET complexes. Cellular phenotypes were rescued upon re-expression of wild-type VPS16. ----- Heterozygous variants, as well as a homozygous missense variant (c.156C>A) found in a consanguineous Chinese family (PMID:27174565), have been found to cause dystonia with variable onset (OMIM:619291). It has been suggested that the discrepancies in patient phenotypes are due to different mechanisms of pathogenicity, where variants causing dystonia do not affect the levels of endolysosomal tethering (HOPS/CORVET) complexes. More research is needed to clarify the mechanisms underlying VPS16-related dystonia as only limited functional data is currently available - Steel et al. 2020 (PMID:32808683) did perform electron microscopic studies of lymphocytes and fibroblasts derived from 2 unrelated patients, which showed vacuolar abnormalities suggestive of impaired lysosomal function. Sources: Literature |
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| Lysosomal storage disorder v1.40 | IDS | Sarah Leigh Phenotypes for gene: IDS were changed from Mucopolysaccharidosis II 309900 to Mucopolysaccharidosis II OMIM:309900; mucopolysaccharidosis type 2 MONDO:0010674 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lysosomal storage disorder v0.8 | HYAL1 | Sarah Leigh Added comment: Comment on list classification: Comments from Dr Clare E Beesley, Clinical Scientist, London North Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust: 2 unrelated families that have variants (PMIDs 10339581, 21559944), also have a confirmed enzyme diagnosis and there is a mouse model that shows similar features (PMID 26322170). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lysosomal storage disorder v0.3 | IDS | Emma Ashton reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lysosomal storage disorder v0.3 | IDS | Carol Hardy reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Mucopolysaccharidosis II 309900; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lysosomal storage disorder v0.2 | IDS |
Ivone Leong gene: IDS was added gene: IDS was added to Lysosomal storage disorder. Sources: North London GLH,Expert Review Green,Wessex and West Midlands GLH,NHS GMS Mode of inheritance for gene: IDS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: IDS were set to Mucopolysaccharidosis II 309900 |
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