RESUMEN
Microscopically visible rearrangements of chromosome 4p includes the two well known abnormalities: partial trisomy 4p, and deletions of the Wolf-Hirschhorn critical regions 1 and 2 (WHSCR 1 and WHSCR2, respectively), which cause well-defined phenotypes including minor anomalies, and developmental delay/intellectual disability. In contrast small duplications of 4p are rare but with the advent of microarray techniques a few cases have been reported in recent years. Here we describe a 3 Mb duplication at 4p16.3 segregating with a characteristic phenotype, macrocephaly, speech delay and mild intellectual disability in a three generation family.
Asunto(s)
Duplicación Cromosómica , Cromosomas Humanos Par 4 , Discapacidad Intelectual/genética , Trastornos del Desarrollo del Lenguaje/genética , Megalencefalia/genética , No Disyunción Genética , Niño , Mapeo Cromosómico , Hibridación Genómica Comparativa , Femenino , Humanos , Hibridación Fluorescente in Situ , Discapacidad Intelectual/diagnóstico , Trastornos del Desarrollo del Lenguaje/diagnóstico , Megalencefalia/diagnóstico , Linaje , FenotipoRESUMEN
The detection of chromosomal abnormalities in patients with mental retardation (MR) and dysmorphic features increases with improvements of molecular cytogenetic methods. We report on six patients referred for detailed characterization of chromosomal abnormalities (four translocations, one inversion, one deletion) detected by conventional cytogenetics, in whom metaphase CGH revealed imbalances not involved in the initially detected rearrangements. The detected abnormalities were validated by real-time PCR. Parents were investigated by CGH in four cases. The genomic screening revealed interstitial deletions of 2q33.2-q34, 3p21, 4q12-q13.1, 6q25, 13q22.2-q31.1, and 14q12. The estimated minimum sizes of the deletions ranged from 2.65 to 9.27 Mb. The CGH assay did not reveal imbalances that colocalized with the breakpoints of the inversion or the translocations. The deletion of 6q included ESR1, in which polymorphisms are associated with variation of adult height. FOXG1B, known to be involved in cortical development, was located in the 14q deletion. The results illustrate that whole-genome molecular cytogenetic analysis of phenotypically affected patients with abnormal conventional karyotypes may detect inapparent molecular cytogenetic abnormalities in patients with microscopic chromosomal abnormalities and that these data provide additional information of clinical importance.