Genotypic-Phenotypic Correlations of Hereditary Hyperferritinemia-Cataract Syndrome: Case Series of Three Brazilian Families.

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare, frequently misdiagnosed, autosomal dominant disease caused by mutations in the FTL gene. It causes bilateral pediatric cataract and hyperferritinemia without iron overload. The objective of this case series, describing three Brazilian families, is to increase awareness of HHCS, as well as to discuss possible phenotypic interactions with concurrent mutations in HFE, the gene associated with autosomal recessive inheritance hereditary hemochromatosis. Whole-exome sequencing was performed in eight individuals with HHCS from three different families, as well as one unaffected member from each family for trio analysis-a total of eleven individuals. Ophthalmological and clinical genetic evaluations were conducted. The likely pathogenic variant c.-157G>A in FTL was found in all affected individuals. They presented slowly progressing bilateral cataract symptoms before the age of 14, with a phenotype of varied bilateral diffuse opacities. Hyperferritinemia was present in all affected members, varying from 971 ng/mL to 4899 ng/mL. There were two affected individuals with one concurrent pathogenic variant in HFE (c.187C>G, p.H63D), who were also the ones with the highest values of serum ferritin in our cohort. Few publications describe individuals with pathogenic mutations in both FTL and HFE genes, and further studies are needed to assess possible phenotypic interactions causing higher values of hyperferritinemia.

Novel Mutation in CRYBB3 Causing Pediatric Cataract and Microphthalmia.

Up to 25% of pediatric cataract cases are inherited, with half of the known mutant genes belonging to the crystallin family. Within these, crystallin beta B3 (CRYBB3) has the smallest number of reported variants. Clinical ophthalmological and genetic-dysmorphological evaluation were performed in three autosomal dominant family members with pediatric cataract and microphthalmia, as well as one unaffected family member. Peripheral blood was collected from all participating family members and next-generation sequencing was performed. Bioinformatics analysis revealed a novel missense variant c.467G>A/p.Gly156Glu in CRYBB3 in all family members with childhood cataract. This variant is classified as likely pathogenic by ACMG, and no previous descriptions of it were found in ClinVar, HGMD or Cat-Map. The only other mutation previously described in the fifth exon of CRYBB3 is a missense variant that causes a change in amino acid from the same 156th amino acid to arginine and has been associated with pediatric cataract and microphthalmia. To the best of our knowledge, this is the first time the c.467G>A/p.Gly156Glu variant is reported and the second time a mutation in CRYBB3 has been associated with microphthalmia.

Cardiometabolic risk factors and Framingham Risk Score in severely obese patients: Baseline data from DieTBra trial.

BACKGROUND AND AIMS: Little is known about differences of cardiometabolic risk factors (CMRF) and the function of Framingham Risk Score (FRS) within severe obesity, thus we aimed to study not only CMRF and FRS, but to determine significant differences between BMI ranges within severe obesity. METHODS AND RESULTS: In this baseline analysis of the Traditional Brazilian Diet (DieTBra) Trial, several CMRF were assessed in 150 adult patients in two BMI ranges: 35.0-44.9 kg/m2 (n = 76) and ≥45 kg/m2 (n = 74). Body composition was evaluated by multifrequency bioelectrical impedance analysis to measure the percent of body fat, visceral fat area and waist circumference. Pearson's Chi-squared, Fisher's Exact, Student's t-test, and Mann-Whitney's test were used in the statistical analysis with a 5% significance level. Hypertension, C-reactive protein, systolic and diastolic blood pressure and positive family history for heart diseases were more prevalent in BMI ≥45.0 kg/m2 (p < 0.05). Mean values of waist circumference, body fat %, visceral fat area, and systolic blood pressure were significantly higher in patients with BMI ≥45.0 kg/m2. Regarding the function of FRS, 40.0% of the patients were at high risk. No differences were found for diabetes, lifestyle, lipid parameters, and FRS within different BMI ranges, except for dyslipidemia, significantly higher among participants with BMI 35.0-44.9 kg/m2. CONCLUSION: BMI >45 kg/m2 was associated with higher prevalence of hypertension, systolic and diastolic blood pressure, C-reactive protein, waist circumference, body fat % and family history of heart diseases, enhancing the risk for the occurrence of cardiovascular diseases.