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| Lipodystrophy_Lipoatrophy v1.35 | ADRA2A | Chirag Patel Marked gene: ADRA2A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lipodystrophy_Lipoatrophy v1.35 | ADRA2A | Chirag Patel Gene: adra2a has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lipodystrophy_Lipoatrophy v1.35 | ADRA2A |
Chirag Patel gene: ADRA2A was added gene: ADRA2A was added to Lipodystrophy_Lipoatrophy. Sources: Genomics England PanelApp Mode of inheritance for gene: ADRA2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ADRA2A were set to 27376152 Phenotypes for gene: ADRA2A were set to Lipodystrophy, familial partial, type 8, OMIM #620679 Review for gene: ADRA2A was set to RED Added comment: 3 affected members of an African American family with onset of atypical partial lipodystrophy around 13 to 15 years of age. As adults, all developed diabetes, hypertension, and hyperlipidemia with increased triglycerides. WES identified a heterozygous missense variant in ADRA2A (L68F), which was absent in ExAC or dbSNP databases and segregated with the disorder in the family. Two clinically unaffected children (3 and 8 years of age) who were younger than the age of symptom onset also carried the variant. Expression of the variant in HEK293 cells showed that the mutant ADRA2A protein was expressed and localized normally to the plasma membrane, but caused slightly increased cAMP production compared to wildtype. Differentiated adipose cells (3T3-L1) transfected with the mutation had a higher rate of basal lipolysis compared to controls, as evidenced by glycerol release. Synthesis of cAMP and lipolysis in cells carrying the variant were resistant to suppression by clonidine and not sensitive to yohimbine, suggesting that the variant results in a loss of function. The findings suggested that excessive lipolysis from certain adipose tissue deposits is the main mechanism causing the disorder. Sources: Genomics England PanelApp |
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