RESUMEN

Warburg-Micro syndrome (WARBM) is an autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy and central nervous system malformations. This syndrome is caused by mutations in the RAB3GAP1/2 and RAB18 genes, part of the Rab family, and in the TBC1D20 gene, which contributes to lipid droplet formation/metabolism. Here we present a patient with clinical diagnosis of WARBM syndrome, who did not have mutations in either the RAB3GAP1/2 genes, in the main exons of RAB18, nor in the TBC1D20 gene. However, the analysis with CGH-array detected a 9.6 Mb deletion at 1q43-qter. We performed a genotype-phenotype correlation using 20 previously published patients in whom the coordinates of the deleted regions were defined. The comparative analysis revealed that the current patient and three of the other 20 patients share the loss of six genes, four of which are related with the family of G proteins, and are strongly expressed in the brain, retina, heart and kidney. Consequently, their haploinsufficiency may result in different combinations of clinical alterations, including some of those of WARBM syndrome. In addition, the haploinsufficiency of other genes may contribute to other defects and clinical variability. Additionally, for the genotype-phenotype correlation, one must also consider molecular pathways that can result in the observed alterations. To early confirm a genetic diagnosis is essential for the patient and family. The current patient was considered as having a recessive syndrome, but since he had a "de novo" deletion, there was not an increased recurrence risk.

Asunto(s)

Anomalías Múltiples/genética , Catarata/congénito , Córnea/anomalías , Haploinsuficiencia , Hipogonadismo/genética , Discapacidad Intelectual/genética , Microcefalia/genética , Atrofia Óptica/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/patología , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Catarata/diagnóstico , Catarata/genética , Catarata/patología , Deleción Cromosómica , Cromosomas Humanos Par 1/genética , Hibridación Genómica Comparativa , Córnea/patología , Citocinas , Análisis Mutacional de ADN , Exones , Forminas , Estudios de Asociación Genética , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/patología , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/patología , Péptidos y Proteínas de Señalización Intercelular/deficiencia , Péptidos y Proteínas de Señalización Intercelular/genética , Masculino , Microcefalia/diagnóstico , Microcefalia/patología , Proteínas de Microfilamentos/deficiencia , Proteínas de Microfilamentos/genética , Proteínas Nucleares/deficiencia , Proteínas Nucleares/genética , Atrofia Óptica/diagnóstico , Atrofia Óptica/patología , Proteínas RGS/deficiencia , Proteínas RGS/genética , Receptor Muscarínico M3 , Receptores Muscarínicos/deficiencia , Receptores Muscarínicos/genética , Opsinas de Bastones/deficiencia , Opsinas de Bastones/genética