Investigating the spectrum of genome copy number variations in individuals with microcephaly or macrocephaly phenotypes

• Grant number: 20/15552-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2021
• End date: July 31, 2022
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Ana Cristina Victorino Krepischi
• Grantee: Giovanna Civitate Bastos
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Microcephaly and macrocephaly are pathological phenotypes mainly resulting from changes in cranial size/volume. These changes may be a consequence of environmental factors, such as intrauterine or congenital infections, teratogenic exposures or vascular injuries, as well as driven by genetic causes, which include mutations in single genes, copy number variations (CNVs), and major structural chromosomal rearrangements and aneuploidies. With the emergence of molecular techniques for chromosomal analysis, such as chromosomal microarray analysis (CMA), the importance of the contribution of CNVs to human phenotypic variability, from the spectrum of normal variability to disease phenotypes, has become evident. It is estimated that approximately 20% of the cases of genetic congenital diseases have a causal association with pathogenic CNVs, especially those related to neurodevelopmental disorders, including the aforementioned phenotypes of microcephaly and macrocephaly. In addition to performing a literature review on the subject, we will seek to explore the genetic heterogeneity associated with the microcephaly and macrocephaly. We intend to delineate the spectrum of genomic loci in which CNVs occur in association with these phenotypes, by investigating patients whose clinical and phenotypic data are deposited in the public database DECIPHER, which has more than 37,200 records; and also compiling over 3,000 cases from the Human Genetics Laboratory of the Institute of Biosciences (USP) previously investigated by CMA.

Scientific publications

(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)

TOLEZANO, GIOVANNA CANTINI; BASTOS, GIOVANNA CIVITATE; DA COSTA, SILVIA SOUZA; FREIRE, BRUNA LUCHEZE; HOMMA, THAIS KATAOKA; HONJO, RACHEL SAYURI; YAMAMOTO, GUILHERME LOPES; PASSOS-BUENO, MARIA RITA; KOIFFMANN, CELIA PRISZKULNIK; KIM, CHONG AE; et al. Burden of Rare Copy Number Variants in Microcephaly: A Brazilian Cohort of 185 Microcephalic Patients and Review of the Literature. JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS, v. N/A, p. 32-pg., 2022-12-11. (20/15552-2)