Germline Mutations in Familial Papillary Thyroid Cancer.

Thyroid cancer, predominantly of papillary histology (PTC), is a common cancer mostly diagnosed sporadically. Hereditary PTC is encountered in ~ 5% of cases and may present at an earlier age, with greater risks of metastasis and recurrence, compared with sporadic cases. The molecular basis of hereditary PTC is unknown in most cases. In this study, the genetic basis of hereditary PTC in three Brazilian families was investigated. Whole exome sequencing (WES) was carried out for probands in each family, and validated, pathogenic/likely pathogenic sequence variants (P/LPSVs) were genotyped in additional family members to establish their putative pathogenic role. Overall, seven P/LPSVs in seven novel genes were detected: p.D283N*ANXA3, p.Y157S*NTN4, p.G172W*SERPINA1, p.G188S*FKBP10, p.R937C*PLEKHG5, p.L32Q*P2RX5, and p.Q76*SAPCD1. These results indicate that these novel genes are seemingly associated with hereditary PTC, but extension and validation in other PTC families are required.

The contribution of FTO and UCP-1 SNPs to extreme obesity, diabetes and cardiovascular risk in Brazilian individuals.

BACKGROUND: Obesity has become a common human disorder associated with significant morbidity and mortality and adverse effects on quality of life. Sequence variants in two candidate genes, FTO and UCP-1, have been reported to be overrepresented in obese Caucasian population. The association of these genes polymorphisms with the obesity phenotype in a multiethnic group such as the Brazilian population has not been previously reported. METHODS: To assess the putative contribution of both FTO and UCP-1 to body mass index (BMI) and cardiovascular risk we genotyped SNPs rs9939609 (FTO) and rs6536991, rs22705565 and rs12502572 (UCP-1) from 126 morbidly obese subjects (BMI 42.9 ± 5.6 kg/m2, mean ± SE) and 113 normal-weight ethnically matched controls (BMI 22.6 ± 3.5 kg/m2, mean ± SE). Waist circumference, blood pressure, glucose and serum lipids were also measured. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphism (indels) for ethnic assignment and to estimate the proportion of European, African and Amerindian biogeographical ancestry in the Brazilian population. RESULTS: Cases did not differ from controls in the proportions of genomic ancestry. The FTO SNP rs9939609 and UCP-1 SNP rs6536991 were significantly associated with BMI (p= 0.04 and p<0.0001 respectively). An allele dose dependent tendency was observed for BMI for rs6536991 sample of controls. No other significant associations between any SNP and hypertension, hyperlipidemia and diabetes were noted after correction for BMI and no significant synergistic effect between FTO and UCP-1 SNPs with obesity were noted. There was not an association between rs9939609 (FTO) and rs6536991 (UCP-1) in with maximum weight loss after 1 year in 94 obese patients who underwent bariatric surgery. CONCLUSION: Our data are consistent with FTO rs9939609 and UCP-1 rs6536991 common variants as contributors to obesity in the Brazilian population.

[Beriberi after bariatric surgery: not an unusual complication. Report of two cases and literature review]. / Beribéri pós bypass gástrico: uma complicação não tão rara. Relato de dois casos e revisão da literatura.

The number of patients submitted to bariatric surgery to treat morbid obesity is increasing, therefore, some nutritional deficiencies, with which many physicians are no longer familiarized, are reappearing. Postoperatively, many nutritional disorders may occur, one of them is thiamine deficiency (beriberi). The thiamine and/or vitamin B12 deficiency can correspond to 40% of the neuropathy cases after bariatric surgery. Two patients with the clinic of peripheral neuropathy and Wernicke-Korsakoff syndrome will be reported. Some months after the surgery, they presented prostration, depression, mental confusion and nystagmus, associated with pain and paresthesia in limbs (especially lower limbs). With the diagnostic hypothesis of beriberi, the treatment with thiamine started. One of the patients presented complete improvement of the neurological symptoms, however the other one remained with motor deficiency, exactly the one who spent a longer period of time between the symptoms appearance and the treatment beginning. These cases serve to alert us about the importance of nutritional vigilance after bariatric surgery.

Beribéri pós bypass gástrico: uma complicação não tão rara. Relato de dois casos e revisão da literatura / Beriberi after bariatric surgery: not an unusual complication. Report of two cases and literature review

É crescente o número de pacientes submetidos à cirurgia bariátrica para tratamento da obesidade mórbida; devido a isso, estão reaparecendo deficiências nutricionais com as quais muitos médicos já não estão familiarizados. No pós-operatório, podem ocorrer vários distúrbios nutricionais, sendo um deles a deficiência de tiamina (beribéri). A deficiência de tiamina e/ou vitamina B12 pode corresponder a 40 por cento dos casos de neuropatia após a cirurgia bariátrica. Serão descritos dois pacientes com a clínica de neuropatia periférica e síndrome de Wernicke-Korsakoff. Alguns meses após a cirurgia, eles apresentaram prostração, depressão, confusão mental e nistagmo, associados a dor e parestesia dos membros (principalmente inferiores). Com a hipótese diagnóstica de beribéri, foi iniciado o tratamento com tiamina. Um dos pacientes apresentou melhora completa do quadro neurológico, porém o outro permaneceu com déficit motor, sendo aquele em que decorreu o maior tempo entre o aparecimento dos sintomas e o início do tratamento. Estes casos servem para nos alertar sobre a importância da vigilância nutricional após a cirurgia bariátrica.