RESUMEN
7qter deletion syndrome includes prenatal and/or postnatal growth retardation, microcephaly, psychomotor delay or mental retardation and a characteristic dysmorphism. If clinical features are well described, the molecular mechanisms underlying the 7qter deletion syndrome remain unknown. Those deletions usually arise de novo. Here, we describe a young boy with an abnormal phenotype consistent with a 7qter deletion syndrome. High resolution genomic analysis (Affymetrix Human Genome Wide SNP 6.0) revealed a 7q36.3 deletion encompassing NCAPG2, ESYT2, WDR60 and VIPR2, inherited from his asymptomatic father and paternal grandfather. In addition, the patient also harbored a MCPH1 deletion inherited from his healthy mother. Combined NCAPG2 and MCPH1 deletions were correlated with low mRNA levels and protein expression in the patient. MCPH1 and NCAPG2 proteins interaction is known to control chromosome structure and we thus propose that double heterozygosity for null mutations of those two genes of the Condensin II system contribute to mental deficiency with severe microcephaly phenotype.
Asunto(s)
Adenosina Trifosfatasas/genética , Proteínas Cromosómicas no Histona/metabolismo , Proteínas de Unión al ADN/genética , Eliminación de Gen , Discapacidad Intelectual/genética , Microcefalia/genética , Complejos Multiproteicos/genética , Proteínas del Tejido Nervioso/genética , Adenosina Trifosfatasas/metabolismo , Proteínas de Ciclo Celular , Niño , Proteínas Cromosómicas no Histona/genética , Cromosomas Humanos Par 7/genética , Proteínas del Citoesqueleto , Proteínas de Unión al ADN/metabolismo , Sitios Genéticos/genética , Heterocigoto , Humanos , Discapacidad Intelectual/diagnóstico , Masculino , Microcefalia/diagnóstico , Complejos Multiproteicos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Linaje , SíndromeRESUMEN
"FOXG1 syndrome" includes postnatal microcephaly, severe intellectual disability with absence of language and agenesis of the corpus callosum. When the syndrome is associated with large 14q12q13 deletions, the patients present characteristic facial dysmorphism. Although all reports were based on genomic analysis, recently a FOXG1 regulatory elements deletion, associated with down regulated mRNA, suggested an implication of FOXG1 pathway. Herein, we report on a young boy with a phenotype consistent with a FOXG1 syndrome. He had a de novo translocation t(6;14)(q22.1;q12) associated with a heterozygous 14q12.2q13 deletion encompassing FOXG1. Subsequently, we investigated his transcriptomic profile on lymphoblastoïd cell lines and/or fibroblasts and showed that FOXG1 was commonly down-regulated. Moreover, several other FOXG1 pathway genes were also disturbed. Our data and review of previous reports highlight dysregulation of FOXG1 pathway as the cause of the "FOXG1 syndrome" developmental disorder.
