Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPTOLEZANO, Giovanna CantiniBASTOS, Giovanna CivitateCOSTA, Silvia Souza daFREIRE, Bruna LuchezeHOMMA, Thais KataokaHONJO, Rachel SayuriYAMAMOTO, Guilherme LopesPASSOS-BUENO, Maria RitaKOIFFMANN, Celia PriszkulnikKIM, Chong AeVIANNA-MORGANTE, Angela MariaJORGE, Alexander Augusto de LimaBERTOLA, Debora RomeoROSENBERG, CarlaKREPISCHI, Ana Cristina Victorino2024-04-052024-04-052024JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS, v.54, n.3, p.1181-1212, 20240162-3257https://observatorio.fm.usp.br/handle/OPI/58948Microcephaly presents heterogeneous genetic etiology linked to several neurodevelopmental disorders (NDD). Copy number variants (CNVs) are a causal mechanism of microcephaly whose investigation is a crucial step for unraveling its molecular basis. Our purpose was to investigate the burden of rare CNVs in microcephalic individuals and to review genes and CNV syndromes associated with microcephaly. We performed chromosomal microarray analysis (CMA) in 185 Brazilian patients with microcephaly and evaluated microcephalic patients carrying < 200 kb CNVs documented in the DECIPHER database. Additionally, we reviewed known genes and CNV syndromes causally linked to microcephaly through the PubMed, OMIM, DECIPHER, and ClinGen databases. Rare clinically relevant CNVs were detected in 39 out of the 185 Brazilian patients investigated by CMA (21%). In 31 among the 60 DECIPHER patients carrying < 200 kb CNVs, at least one known microcephaly gene was observed. Overall, four gene sets implicated in microcephaly were disclosed: known microcephaly genes; genes with supporting evidence of association with microcephaly; known macrocephaly genes; and novel candidates, including OTUD7A, BBC3, CNTN6, and NAA15. In the review, we compiled 957 known microcephaly genes and 58 genomic CNV loci, comprising 13 duplications and 50 deletions, which have already been associated with clinical findings including microcephaly. We reviewed genes and CNV syndromes previously associated with microcephaly, reinforced the high CMA diagnostic yield for this condition, pinpointed novel candidate loci linked to microcephaly deserving further evaluation, and provided a useful resource for future research on the field of neurodevelopment.engrestrictedAccessCMACNVMicrocephalyNeurodevelopmental disordersOTUD7ABBC3CNTN6NAA15congenital heart-diseaseintellectual disabilitychromosomal microarraymicrodeletion syndromearray-cghphenotypedeletionduplicationmutationsgenesarticleCopyright SPRINGER/PLENUM PUBLISHERS10.1007/s10803-022-05853-zPsychology, Developmental1573-3432