Detection and consequences of imbalances in the human genome

• Grant number: 18/08890-9
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2018
• End date: September 30, 2021
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Társis Antônio Paiva Vieira
• Grantee: Társis Antônio Paiva Vieira
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Vera Lúcia Gil da Silva Lopes

Abstract

Genomic imbalances (GIs) are an important class of variation in the human genome. Many of them are related to diseases and responsible for the phenotype in a substantial number (10 - 20%) of individuals with congenital anomalies (CA) and (or) intellectual disability (ID)/ developmental delay (DD). Currently, the chromosomal microarray analysis (CMA) is pointed as a first tier for the molecular diagnosis of this group of patients. Nevertheless, studies published recently have been suggested that the whole exome sequencing (WES) could substitute the CMA as the first diagnostic test, considering that the latter is able to identify both small nucleotide variants (SNVs) and GIs, in a single experiment. However, to date, there are few studies with patient groups and there is not a consensus about this substitution yet. On the other hand, a constant challenge in the interpretation of GIs detected by CMA, in individuals with CA and (or) ID/ DD, is the identification of variants of unknown significance (VUS). Recently, a study suggested that the WES would be necessary to clarify cases with ID/ DD and VUS. The aims of this project are: to perform the WES and search for SNVs related to the phenotype in individuals with CA and (or) ID/ DD, and VUS detected previously by CMA; and to identify the GIs detected previously by the CMA, performing GIs analysis in the WES data, in the same group of individuals. 50 individuals with CA and (or) ID/ DD and VUS detected by CMA will be selected. The WES will be performed, followed by two analyses: the search for SNVs related to the phenotype and the search for GIs in the WES data. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CORREIA-COSTA, GABRIELA ROLDAO; DE LEEUW, NICOLE; PFUNDT, ROLPH; SGARDIOLI, ILARIA CRISTINA; DOS SANTOS, ANA PAULA; SANTOS, MARILZA DE LIMA; GIL-DA-SILVA-LOPES, VERA LUCIA; VIEIRA, TARSIS PAIVA. Biallelic frameshift variant in the TBC1D2B gene in two siblings with progressive gingival overgrowth, fibrous dysplasia of face, and mental deterioration. Clinical Genetics, v. 102, n. 6, p. 6-pg., 2022-09-07. (12/51799-6, 18/08890-9)

GABRIELA ROLDÃO CORREIA-COSTA; ILÁRIA CRISTINA SGARDIOLI; ANA PAULA DOS SANTOS; TÂNIA KAWASAKI DE ARAUJO; RODRIGO SECOLIN; ISCIA LOPES-CENDES; VERA LÚCIA GIL-DA-SILVA-LOPES; TÁRSIS PAIVA VIEIRA. Increased runs of homozygosity in the autosomal genome of Brazilian individuals with neurodevelopmental delay/intellectual disability and/or multiple congenital anomalies investigated by chromosomal microarray analysis. GENETICS AND MOLECULAR BIOLOGY, v. 45, n. 1, 2022-02-28. (18/08890-9, 12/51799-6)

CORREIA-COSTA, GABRIELA ROLDAO; DOS SANTOS, ANA MONDADORI; DE LEEUW, NICOLE; RIGATTO, SUMARA ZUANAZI PINTO; BELANGERO, VERA MARIA SANTORO; STEINER, CARLOS EDUARDO; GIL-DA-SILVA-LOPES, VERA LUCIA; VIEIRA, TARSIS PAIVA. Dual Molecular Diagnoses of Recessive Disorders in a Child from Consanguineous Parents: Case Report and Literature Review. GENES, v. 13, n. 12, p. 11-pg., 2022-12-01. (18/08890-9)

CORREIA-COSTA, G. R.; SPINELI-SILVA, S.; SGARDIOLI, I. C.; DOS-SANTOS, A. P.; MARQUES-PROTA, J. R.; SECOLIN, R.; LEIJSTEN, N.; RUITERKAMP-VERSTEEG, M. H. A.; DE LEEUW, N.; LOPES-CENDES, I.; et al. Report and investigation of regions of homozygosity in the autosomal genome of Brazilian individuals with intellectual disability and (or) multiple congenital anomalies previously investigated by chromosomal microarray analysis. European Journal of Human Genetics, v. 28, n. SUPPL 1, p. 1-pg., 2020-12-01. (18/08890-9)

SPINELI-SILVA, S.; DE LEEUW, N.; DOS SANTOS, A. P.; LEIJSTEN, N.; RUITERKAMP-VERSTEEG, M. H. A.; PROTA, J. R. M.; MACIEL-GUERRA, A. T.; MARQUES-DE-FARIA, A.; STEINER, C. E.; GIL-DA-SILVA-LOPES, V. L.; et al. Whole Exome Sequencing in Brazilian individuals with intellectual disability, Neurodevelopmental Delay and (or) Multiple Congenital Anomalies with Copy Number Variants of Uncertain Clinical Significance detected by Chromosomal Microarray Analysis. European Journal of Human Genetics, v. 28, n. SUPPL 1, p. 1-pg., 2020-12-01. (18/08890-9)