MKS1 Gene Curation
- Andrea Oza
Analytics
Gene-disease assertions not curated here (add link or write note): Meckel and Joubert syndromes were lumped together given the phenotypic overlap and no difference in mechanism found (LOF established for both). Bardet-Biedl is curated as limited by Invitae in GenCC, but it also has phenotype overlap, so it is unclear whether this is a separate entity.
Disease | MKS1- Related disorders(Meckel syndrome, Joubert syndrome) |
|---|---|
Inheritance | Autosomal recessive |
Prevalence | Meckel Gruber syndrome is 1 in 13,250 to 1 in 140,000 live births according to PMID: 24082939 Source: |
Rapid or full curation? | Rapid Full |
ClinGen - dosage (curation status = reopened). GenCC - Strong for Meckel and Joubert syndrome (invitae), limited for Bardet-Biedl. BabySeq - strong for Meckel syndrome (PMID: 6486167, 17377820, 16415886, 17397051, 18327255, 17437276) | |
Clinical Validity Scoring Notes and points | Using BabySeq citations listed above. |
Clinical Validity Points Total | N/A |
Clinical Validity Classification Definitive (12pts) Strong (12pts) Moderate (7-11pts) Limited (0.1-6pts) No genetic evidence Refuted Disputed | Strong Source: 6486167, 17377820, 16415886, 17397051, 18327255, 17437276 |
Molecular Mechanism Loss of function Gain of function Dominant negative Unknown Other | Loss of function Sources: 17397051, 19466712, 23351400, 26490104, 33193692 Meckel
Joubert
|
Penetrance Complete (100%) High (≥80%) Moderate (<80% and >20%) Low (≤20%) (list source/PMID) |
Source: |
Age of Onset Congenital Pediatric Adolescent Adulthood Late adulthood (list source/PMID) | Congenital |
Severity | Severe/Lethal |
Clinical Features |
Sources: |
HPO Terms |
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Gene SOPs & Notes | LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant |
Curation Summary | The MKS1 gene is associated with autosomal recessive MKS1-related disorders, which include Meckel syndrome and autosomal recessive Joubert syndrome; these syndromes share overlapping clinical features including central nervous system malformation, renal/liver disease, and polydactyly (PMID: 34359301, 24886560,19466712). Loss of function variants have been reported in both syndromes (PMID: 17397051, 19466712, 23351400, 26490104, 33193692). Joubert syndrome is characterized by cerebellar vermis hypoplasia, cystic kidney disease, liver fibrosis, polydactyly, and retinal dystrophy, intellectual disability, developmental delay, endocrine abnormalities, obesity, ataxia, typical facial features, congenital heart defects, and other findings (PMID: 20301500). Meckel syndrome is a severe/lethal disease characterized by occipital encephalocele, cystic renal dysplasia, and postaxial polydactyly. |
Case ID, Curator name, Date, Jira ticket link | Andrea Oza, 02.22.2024 D-180314734-BH-4039-P-A |