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| Severe early-onset obesity v0.87 | MRAP2 | Zornitza Stark Publications for gene: MRAP2 were set to 26795956 - a rare nonsynonymous variant, p.A40S, was detected in the MRAP2 gene in a 10-year old boy with overall obesity in combination with intellectual disability in a screen of Prader-Willi syndrome (PWS) patients. The clinically diagnosed PWS could not be confirmed molecularly with MS-MLPA and CNV analysis of the 6q14.1 q16.3 region also showed no deletions in this patient. No further family data were available to determine whether the variant segregates with obesity in this family. It was shown to be (probably) damaging by in silico analysis and found in only one European (non-Finnish) individual in the ExAC database (since this database cannot release phenotype information about the screened individuals, no conclusions regarding causality of this variant can be drawn).; 27474872 - screened the entire coding region of MRAP2 for mutations in 184 children and adolescents with extreme obesity and 184 healthy lean controls. Nonsynonymous variants were then genotyped in a larger, independent study group of 300 children and adolescents with extreme obesity and 436 controls. Detected variants were also analyzed in vitro to determine their effects on MC4R signaling: p.Gln174Arg was the only variant to show an effect by reducing MC4R signalling function. Heterozygous variants were described in 4 individuals. For only two (p.Ala137Thr and p.Arg125His) were relatives also available, and the mothers of the probands were also heterozygous and had not/did not display an obesity phenotype. "In sum, our family-based genetic data do not support the relevance of the two presumably benign MRAP2 mutations for the development of obesity, they might even have no influence on body weight regulation...additional functional analyses could well reveal a functional effect of all nonsynonymous MRAP2 mutations." "We detected association of nonsynonymous MRAP2 mutations to obesity (eight carriers of nonsynonymous mutations in 1,334 individuals with obesity vs. zero carriers of nonsynonymous mutations in 1,108 controls, nominal Fisher exact two-sided P<0.005) in a crude meta-analysis on all currently available data."; 23869016 - sequenced the coding region and intron/exon boundaries of MRAP2 in obese and control individuals from the Genetics of Obesity Study (GOOS) cohort and the Swedish obese children s cohort. They describe identifying 4 heterozygous variants in 4 individuals with severe obesity, of which only one was predicted to be damaging (E24X) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe early-onset obesity v0.27 | MC4R | Zornitza Stark Marked gene: MC4R as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe early-onset obesity v0.27 | MC4R | Zornitza Stark Gene: mc4r has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe early-onset obesity v0.27 | MC4R | Zornitza Stark Phenotypes for gene: MC4R were changed from Obesity (BMIQ20), OMIM:618406; {Obesity, resistence to (BMIQ20)}, OMIM:618306 to Obesity (BMIQ20) MIM#618406 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe early-onset obesity v0.26 | MC4R | Zornitza Stark Publications for gene: MC4R were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe early-onset obesity v0.22 | MC4R | Ain Roesley reviewed gene: MC4R: Rating: GREEN; Mode of pathogenicity: None; Publications: 12646665, 34238466, 32805220; Phenotypes: Obesity (BMIQ20) MIM#618406; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe early-onset obesity v0.0 | MRAP2 |
Zornitza Stark gene: MRAP2 was added gene: MRAP2 was added to Severe early-onset obesity. Sources: Genomics England PanelApp,Expert Review Red Mode of inheritance for gene: MRAP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MRAP2 were set to 26795956 - a rare nonsynonymous variant, p.A40S, was detected in the MRAP2 gene in a 10-year old boy with overall obesity in combination with intellectual disability in a screen of Prader-Willi syndrome (PWS) patients. The clinically diagnosed PWS could not be confirmed molecularly with MS-MLPA and CNV analysis of the 6q14.1 q16.3 region also showed no deletions in this patient. No further family data were available to determine whether the variant segregates with obesity in this family. It was shown to be (probably) damaging by in silico analysis and found in only one European (non-Finnish) individual in the ExAC database (since this database cannot release phenotype information about the screened individuals, no conclusions regarding causality of this variant can be drawn).; 27474872 - screened the entire coding region of MRAP2 for mutations in 184 children and adolescents with extreme obesity and 184 healthy lean controls. Nonsynonymous variants were then genotyped in a larger, independent study group of 300 children and adolescents with extreme obesity and 436 controls. Detected variants were also analyzed in vitro to determine their effects on MC4R signaling: p.Gln174Arg was the only variant to show an effect by reducing MC4R signalling function. Heterozygous variants were described in 4 individuals. For only two (p.Ala137Thr and p.Arg125His) were relatives also available, and the mothers of the probands were also heterozygous and had not/did not display an obesity phenotype. "In sum, our family-based genetic data do not support the relevance of the two presumably benign MRAP2 mutations for the development of obesity, they might even have no influence on body weight regulation...additional functional analyses could well reveal a functional effect of all nonsynonymous MRAP2 mutations." "We detected association of nonsynonymous MRAP2 mutations to obesity (eight carriers of nonsynonymous mutations in 1,334 individuals with obesity vs. zero carriers of nonsynonymous mutations in 1,108 controls, nominal Fisher exact two-sided P<0.005) in a crude meta-analysis on all currently available data."; 23869016 - sequenced the coding region and intron/exon boundaries of MRAP2 in obese and control individuals from the Genetics of Obesity Study (GOOS) cohort and the Swedish obese children s cohort. They describe identifying 4 heterozygous variants in 4 individuals with severe obesity, of which only one was predicted to be damaging (E24X) Phenotypes for gene: MRAP2 were set to Prader-Willi syndrome; obesity; {?Obesity, susceptibility to, BMIQ18} |
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| Severe early-onset obesity v0.0 | MC4R |
Zornitza Stark gene: MC4R was added gene: MC4R was added to Severe early-onset obesity. Sources: Genomics England PanelApp,Expert Review Green Mode of inheritance for gene: MC4R was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Phenotypes for gene: MC4R were set to Obesity (BMIQ20), OMIM:618406; {Obesity, resistence to (BMIQ20)}, OMIM:618306 |
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