Burden of Rare Copy Number Variants in Microcephaly: A Brazilian Cohort of 185 Microcephalic Patients and Review of the Literature.

Autor: Tolezano GC; Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, 106 Rua do Matão, São Paulo, SP, 05508-090, Brazil., Bastos GC; Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, 106 Rua do Matão, São Paulo, SP, 05508-090, Brazil., da Costa SS; Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, 106 Rua do Matão, São Paulo, SP, 05508-090, Brazil., Freire BL; Unidade de Endocrinologia Genética (LIM25), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 455 Avenida Doutor Arnaldo, São Paulo, SP, 01246-903, Brazil., Homma TK; Unidade de Endocrinologia Genética (LIM25), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 455 Avenida Doutor Arnaldo, São Paulo, SP, 01246-903, Brazil., Honjo RS; Unidade de Genética do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 647 Avenida Doutor Enéas Carvalho de Aguiar, São Paulo, SP, 05403-900, Brazil., Yamamoto GL; Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, 106 Rua do Matão, São Paulo, SP, 05508-090, Brazil.; Unidade de Genética do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 647 Avenida Doutor Enéas Carvalho de Aguiar, São Paulo, SP, 05403-900, Brazil., Passos-Bueno MR; Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, 106 Rua do Matão, São Paulo, SP, 05508-090, Brazil., Koiffmann CP; Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, 106 Rua do Matão, São Paulo, SP, 05508-090, Brazil., Kim CA; Unidade de Genética do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 647 Avenida Doutor Enéas Carvalho de Aguiar, São Paulo, SP, 05403-900, Brazil., Vianna-Morgante AM; Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, 106 Rua do Matão, São Paulo, SP, 05508-090, Brazil., de Lima Jorge AA; Unidade de Endocrinologia Genética (LIM25), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 455 Avenida Doutor Arnaldo, São Paulo, SP, 01246-903, Brazil., Bertola DR; Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, 106 Rua do Matão, São Paulo, SP, 05508-090, Brazil.; Unidade de Genética do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 647 Avenida Doutor Enéas Carvalho de Aguiar, São Paulo, SP, 05403-900, Brazil., Rosenberg C; Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, 106 Rua do Matão, São Paulo, SP, 05508-090, Brazil., Krepischi ACV; Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, 106 Rua do Matão, São Paulo, SP, 05508-090, Brazil. ana.krepischi@ib.usp.br.; Institute of Biosciences, University of São Paulo, 277 Rua do Matão, São Paulo, SP, 05508-090, Brazil. ana.krepischi@ib.usp.br.
Jazyk: angličtina
Zdroj: Journal of autism and developmental disorders [J Autism Dev Disord] 2024 Mar; Vol. 54 (3), pp. 1181-1212. Date of Electronic Publication: 2022 Dec 11.
DOI: 10.1007/s10803-022-05853-z
Abstrakt: Microcephaly 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.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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