title: Craniosynostosis in 10q26 deletion patients: A consequence of brain underdevelopment or altered suture biology?
abstract: Approximately a hundred patients with terminal 10q deletions have been described. They present with a wide range of clinical features always accompanied by delayed development, intellectual disability and craniofacial dysmorphisms. Here, we report a girl and a boy with craniosynostosis, developmental delay and other congenital anomalies. Karyotyping and molecular analysis including Multiplex Ligation dependent probe amplification (MLPA) and Array Comparative Genomic Hybridization (aCGH) were performed in both patients. We detected a 13.1 Mb pure deletion at 10q26.12-q26.3 in the girl and a 10.9 Mb pure deletion at 10q26.13-q26.3 in the boy, both encompassing about 100 genes. The clinical and molecular findings in these patients reinforce the importance of the DOCK1 smallest region of overlap I (SRO I), previously suggested to explain the clinical signs, and together with a review of the literature suggest a second 3.5 Mb region important for the phenotype (SRO II). Genotype-phenotype correlations and literature data suggest that the craniosynostosis is not directly related to dysregulated signaling in suture development, but may be secondary to alterations in brain development instead. Further, genes at 10q26 may be involved in the molecular crosstalk between brain and cranial vault.
authors.affiliation: Programa de Graduação em Biotecnologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo (UFES), Vitória, Espírito Santo, Brasil.|Laboratório de Genética Humana e Molecular, Centro de Pesquisa ICALP, Escola Superior de Ciências da Santa Casa de Misericórdia (EMESCAM), Vitória, Espírito Santo, Brasil.
authors.forename: Ágatha Cristhina
authors.initials: ÁC
authors.lastname: Faria
authors.affiliation: Laboratório de Genética e Biologia Molecular, Associação Educacional de Vitória, Vitória, Espírito Santo, Brasil.
authors.forename: Eliete
authors.initials: E
authors.lastname: Rabbi-Bortolini
authors.affiliation: Divisão de Genética Clínica, Hospital Estadual Infantil Nossa Senhora da Glória (HEINSG), Vitória, Espírito Santo, Brasil.
authors.forename: Maria R G O
authors.initials: MRGO
authors.lastname: Rebouças
authors.affiliation: Unidade de Neonatologia, Hospital Santa Casa de Misericórdia, Vitória, Espírito Santo, Brasil.
authors.forename: Andréia L A
authors.initials: ALA
authors.lastname: de S Thiago Pereira
authors.affiliation: Unidade de Neonatologia, Hospital Santa Casa de Misericórdia, Vitória, Espírito Santo, Brasil.
authors.forename: Milena G Tonini
authors.initials: MGT
authors.lastname: Frasson
authors.affiliation: Centro de Pesquisas Sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto De Biociências, Universidade de São Paulo (USP), São Paulo, São Paulo, Brasil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Atique
authors.affiliation: Centro de Pesquisas Sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto De Biociências, Universidade de São Paulo (USP), São Paulo, São Paulo, Brasil.
authors.forename: Naila Cristina V
authors.initials: NCV
authors.lastname: Lourenço
authors.affiliation: Centro de Pesquisas Sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto De Biociências, Universidade de São Paulo (USP), São Paulo, São Paulo, Brasil.
authors.forename: Carla
authors.initials: C
authors.lastname: Rosenberg
authors.affiliation: Centro de Pesquisas Sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto De Biociências, Universidade de São Paulo (USP), São Paulo, São Paulo, Brasil.
authors.forename: Gerson S
authors.initials: GS
authors.lastname: Kobayashi
authors.affiliation: Centro de Pesquisas Sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto De Biociências, Universidade de São Paulo (USP), São Paulo, São Paulo, Brasil.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Passos-Bueno
authors.affiliation: Programa de Graduação em Biotecnologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo (UFES), Vitória, Espírito Santo, Brasil.|Laboratório de Genética Humana e Molecular, Centro de Pesquisa ICALP, Escola Superior de Ciências da Santa Casa de Misericórdia (EMESCAM), Vitória, Espírito Santo, Brasil.
authors.forename: Flávia Imbroisi Valle
authors.initials: FIV
authors.lastname: Errera
mesh_terms: D000328:Adult; D001921:Brain / Q000002:abnormalities* / Q000473:pathology; D002872:Chromosome Deletion; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D003398:Craniosynostoses / Q000209:etiology* / Q000473:pathology; D019066:Facies; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007859:Learning Disabilities / Q000209:etiology* / Q000473:pathology; D008297:Male; D011379:Prognosis; D013537:Sutures / Q000009:adverse effects*
keywords: 10q26; EBF3; HMX2; HMX3; array CGH; brain development; craniofacial dysmorphisms; synostosis