SANDRO FELIX PERAZZIO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
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- Frequency of carriers for rare metabolic diseases in a Brazilian cohort of 320 patients(2022) QUAIO, Caio Robledo D'Angioli Costa; MOREIRA, Caroline Monaco; CHUNG, Christine Hsiaoyun; PERAZZIO, Sandro Felix; DUTRA, Aurelio Pimenta; KIM, Chong AeBackground Several metabolic disorders follow an autosomal recessive inheritance pattern. Epidemiological information on these disorders is usually limited in developing countries. Our objective is to assess carrier frequencies of rare autosomal recessive metabolic diseases in a cohort of Brazilian patients that underwent molecular investigation with exome sequencing and estimate the overall frequency of these diseases using the Hardy-Weinberg equation. Methods and results We reviewed the molecular findings of 320 symptomatic patients who had carrier status for recessive diseases actively searched. A total of 205 rare variants were reported in 138 different genes associated with metabolic diseases from 156 patients, which represents that almost half (48.8%) of the patients were carriers of at least one heterozygous pathogenic/likely pathogenic (P/LP) variant for rare metabolic disorders. Most of these variants are harbored by genes associated with multisystemic involvement. We estimated the overall frequency for rare recessive metabolic diseases to be 10.96/10,000 people, while the frequency of metabolic diseases potentially identified by newborn screening was estimated to be 2.93/10,000. Conclusions This study shows the potential research utility of exome sequencing to determine carrier status for rare metabolic diseases, which may be a possible strategy to evaluate the clinical and social burden of these conditions at the population level and guide the optimization of health policies and newborn screening programs.
- Frequency of carriers for rare recessive Mendelian diseases in a Brazilian cohort of 320 patients(2021) QUAIO, Caio Robledo D'Angioli Costa; CHUNG, Christine Hsiaoyun; PERAZZIO, Sandro Felix; DUTRA, Aurelio Pimenta; MOREIRA, Caroline Monaco; NOVO FILHO, Gil Monteiro; SACRAMENTO-BOBOTIS, Patricia Rossi; PENNA, Michele Groenner; SOUZA, Rafaela Rogerio Floriano de; CINTRA, Vivian Pedigone; CARNAVALLI, Juliana Emilia Prior; SILVA, Rafael Alves da; PAIXAO, Daniele; BARATELA, Wagner Antonio da Rosa; OLIVATI, Caroline; SPOLADOR, Gustavo Marquezani; SANTOS, Monize Nakamoto Provisor; PINTAO, Maria Carolina; FORNARI, Alexandre Ricardo dos Santos; BURGER, Matheus; RAMALHO, Rodrigo Fernandes; PEREIRA, Otavio Jose Eulalio; FERREIRA, Elisa Napolitano; MITNE-NETO, Miguel; KIM, Chong AeSeveral Mendelian disorders follow an autosomal recessive inheritance pattern. Epidemiological information on many inherited disorders may be useful to guide health policies for rare diseases, but it is often inadequate, particularly in developing countries. We aimed to calculate the carrier frequencies of rare autosomal recessive Mendelian diseases in a cohort of Brazilian patients using whole exome sequencing (WES). We reviewed the molecular findings of WES from 320 symptomatic patients who had carrier status for recessive diseases. Using the Hardy-Weinberg equation, we estimated recessive disease frequencies (q(2)) considering the respective carrier frequencies (2pq) observed in our study. We calculated the sensitivity of carrier screening tests based on lists of genes from five different clinical laboratories that offer them in Brazil. A total of 425 occurrences of 351 rare variants were reported in 278 different genes from 230 patients (71.9%). Almost half (48.8%) were carriers of at least one heterozygous pathogenic/likely pathogenic variant for rare metabolic disorders, while 25.9% of epilepsy, 18.1% of intellectual disabilities, 15.6% of skeletal disorders, 10.9% immune disorders, and 9.1% of hearing loss. We estimated that an average of 67% of the variants would not have been detected by carrier screening panels. The combined frequencies of autosomal recessive diseases were estimated to be 26.39/10,000 (or similar to 0.26%). This study shows the potential research utility of WES to determine carrier status, which may be a possible strategy to evaluate the clinical and social burden of recessive diseases at the population level and guide the optimization of carrier screening panels.
- Parental segregation study reveals rare benign and likely benign variants in a Brazilian cohort of rare diseases(2022) QUAIO, Caio Robledo D'Angioli Costa; CERONI, Jose Ricardo Magliocco; CERVATO, Murilo Castro; THUROW, Helena Strelow; MOREIRA, Caroline Monaco; TRINDADE, Ana Carolina Gomes; FURUZAWA, Cintia Reys; SOUZA, Rafaela Rogerio Floriano de; PERAZZIO, Sandro Felix; DUTRA, Aurelio Pimenta; CHUNG, Christine Hsiaoyun; KIM, Chong AeGenomic studies may generate massive amounts of data, bringing interpretation challenges. Efforts for the differentiation of benign and pathogenic variants gain importance. In this article, we used segregation analysis and other molecular data to reclassify to benign or likely benign several rare clinically curated variants of autosomal dominant inheritance from a cohort of 500 Brazilian patients with rare diseases. This study included only symptomatic patients who had undergone molecular investigation with exome sequencing for suspected diseases of genetic etiology. Variants clinically suspected as the causative etiology and harbored by genes associated with highly-penetrant conditions of autosomal dominant inheritance underwent Sanger confirmation in the proband and inheritance pattern determination because a ""de novo"" event was expected. Among all 327 variants studied, 321 variants were inherited from asymptomatic parents. Considering segregation analysis, we have reclassified 51 rare variants as benign and 211 as likely benign. In our study, the inheritance of a highly penetrant variant expected to be de novo for pathogenicity assumption was considered as a non-segregation and, therefore, a key step for benign or likely benign classification. Studies like ours may help to identify rare benign variants and improve the correct interpretation of genetic findings.
- Exome sequencing of 500 Brazilian patients with rare diseases: what we have learned(2022) QUAIO, Caio Robledo D'Angioli Costa; MOREIRA, Caroline Monaco; CHUNG, Christine Hsiaoyun; PERAZZIO, Sandro Felix; DUTRA, Aurelio Pimenta; KIM, Chong Ae