β-Thalassemia heterozygote state detrimentally affects health expectation

Use of >100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations

“…The p.Gln40Ter mutation is much less prevalent outside of the Western Mediterranean, but has been detected among individuals with beta thalassemia among admixed populations from Central and South America [34,35], which are geographically and genetically similar to some of the Hispanic/Latino samples included in our imputation-based discovery sample. While the individuals carrying the HBB p.Gln40Ter allele in our unselected population-based Hispanic/Latino sample were all imputed heterozygotes (consistent with "thalassemia minor" and generally considered healthy), there is increasing evidence that silent carriers of beta-thalassemia and sickle cell mutations may be at risk for various health-related conditions [36,37]. Due to the relatively small number of Hispanic/Latino individuals with blood cell trait data in TOPMed freeze 5b (n~1,080), including only one heterozygote carrier of rs11549407 in those with blood cell traits measured, we were unable to perform a well-powered replication of the association of rs11549407 with HGB and HCT.…”

Use of >100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations

“…The p.Gln40Ter mutation is much less prevalent outside of the WesternMediterranean, but has been detected among individuals with beta thalassemia among admixed populations from Central and South America(34,35), which are geographically and genetically similar to some of the Hispanic/Latino samples included in our imputation-based discovery sample. While the individuals carrying the HBB p.Gln40Ter allele in our unselected populationbased Hispanic/Latino sample were all imputed heterozygotes (consistent with "thalassemia minor" and generally considered healthy), there is increasing evidence that silent carriers of betathalassemia and sickle cell mutations may be at risk for various health-related conditions(36,37). Due to the relatively small number of Hispanic/Latino individuals with blood cell trait data in TOPMed freeze 5b (n~1,080), including only one heterozygote carrier of rs11549407 in those with blood cell traits measured, we were unable to perform a well-powered replication of the association of rs11549407 with HGB and HCT.…”

Glutaric acidemia type II patient with thalassemia minor and novel electron transfer flavoprotein-A gene mutations: A case report and review of literature

“…In thalassemia minor (Tm), hemoglobin synthesis is decreased, but individuals are generally considered healthy. However, Tm is thought to be a potential risk for cardiovascular, neurological, metabolic, and vascular complications[ 10 ], and as a result of increased iron absorption, ineffective erythropoiesis, erythroid hyperplasia, and decreased antioxidant capacity, Tm affects health expectations[ 10 ]. Coexistence of GAII and thalassemia minor in our patient may make her prone to infections and a decreased tolerance to complications may be expected.…”