RESUMEN
Oculoauriculovertebral spectrum (OAVS) is a clinically and genetically heterogeneous congenital disorder. We performed high density oligonucleotide array-CGH on 86 OAVS patients and identified in 11 patients 12 novel genomic rearrangements (4 deletions and 8 duplications) ranging in size from 2.7 kb to 2.3 Mb. We discuss the potential pathogenic role of these chromosomal aberrations, and describe new candidate regions for OAVS.
Asunto(s)
Aberraciones Cromosómicas , Perfilación de la Expresión Génica , Síndrome de Goldenhar/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Adolescente , Adulto , Biomarcadores/metabolismo , Niño , Preescolar , Estudios de Cohortes , Hibridación Genómica Comparativa , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Adulto JovenRESUMEN
We report a patient presenting with oculoauriculovertebral spectrum and a de novo balanced reciprocal translocation t(9;18)(p23;q12.2). Physical mapping of the translocation breakpoints by fluorescent in situ hybridization showed that the breakpoints are located in two regions encompassing gene deserts. An additional paternally inherited duplication in 18p11.23p11.31 was identified by array-CGH. We discuss the possible involvement of these chromosomal abnormalities in OAVS.
Asunto(s)
Anomalías Múltiples/genética , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 9/genética , Oído/anomalías , Anomalías del Ojo/genética , Pérdida Auditiva Conductiva/genética , Translocación Genética , Preescolar , Aberraciones Cromosómicas , Clonación Molecular , Citogenética , Duplicación de Gen , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Mapeo Físico de CromosomaRESUMEN
We describe a patient presenting with developmental delay, patent foramen ovale, moderate short QT interval, and facial dysmorphism including left microtia, preauricular tag and pit, wide left corner of the mouth, and left hemifacial microsomia, fitting with the oculoauriculovertebral spectrum. We identified a de novo 2.3 Mb deletion in the 12p13.33 region that contains eighteen genes. Amongst those, the WNT5B gene stands out as a possible candidate. However, we did not find any mutation of this gene neither in our patient nor in a series of 53 OAVS patients. The CACNA1C gene is interrupted by the centromeric breakpoint of the deletion and its inactivation probably accounts for the short QT interval of the patient. We speculate that the phenotype of our patient may be explained by the combined effect of the loss of several of the genes contained in the deleted chromosomal segment and of the inactivation of CACNA1C.