Ivone Leong Phenotypes for gene: SH2B1 were changed from obesity; Severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency to obesity; Severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency, MONDO:0017994
Ivone Leong Publications for gene SH2B1 were changed from 26031769 - we performed a mutation screen for variants in the SH2B1 coding region in 581 obese children and adolescents and 433 healthy, lean individuals. Mutation analysis resulted in the identification of fifteen rare non-synonymous heterozygous variants. Several of these were found both in lean and obese subjects, suggesting that these are neutral polymorphisms. However, six private, heterozygous, non-synonymous variations were present in obese children only. Furthermore, we also identified six missense variants solely in lean individuals; 25955518 - GWAS studies have identified an association with adult BMI with a region with high linkage disequilibrium that includes five genes (SH2B1, APOBR, SULT1A1 and SULT1A2, TUFM). This study showed APOBR variants contribute as much as SH2B1 variants to the association; 26075635; 24971614 - "We describe the identification of 4 novel variants in SH2B1 that are present in individuals with obesity and insulin resistance. Some of the variants we found in severely obese individuals are also found in publicly available exomes...However, because BMI and additional phenotypic information for individuals in these datasets are not available, the precise contribution of these variants to obesity remains to be established...These findings suggest that SH2B1 contains a spectrum of common and rare alleles that contribute to BMI and obesity predisposition with a broad range of penetrance, from low to more highly penetrant rare alleles. One variant, A663V, was identified in 14 severely obese individuals in the GOOS cohort as well as in many publically available exomes. In cells, A663V affected the ability of SH2B1 to enhance cell motility in response to GH. Therefore, it is possible that this variant may contribute to the phenotype of variant carriers. These findings suggest that SH2B1 contains a spectrum of common and rare alleles that contribute to BMI and obesity predisposition with a broad range of penetrance, from low to more highly penetrant rare alleles. One variant, A663V, was identified in 14 severely obese individuals in the GOOS cohort as well as in many publically available exomes. In cells, A663V affected the ability of SH2B1 to enhance cell motility in response to GH. Therefore, it is possible that this variant may contribute to the phenotype of variant carriers."; 23160192 - "We identified 300 patients with severe early-onset obesity from the Genetics of Obesity Study (GOOS) cohort (11) with a disproportionate degree of insulin resistance for their obesity, as defined by the presence of acanthosis nigricans, development of type 2 diabetes in early adolescence, and/or markedly elevated plasma insulin (top decile for age, gender, and BMI). Mutations in the genes causing the known monogenic obesity syndromes had been excluded in these patients, as had deletions at 16p11.2 by multiplex ligation–dependent probe amplification (MLPA)." 5 unrelated probands of mixed European descent with heterozygous mutations in SH2B1 were reported to be absent from 500 control subjects. All mutations were inherited from overweight/obese parents, and carriers were hyperphagic and had reduced final height as adults. to 20808231; 24971614; 28663568; 23160192