High resolution microarray CGH and MLPA analysis for improved genotype/phenotype evaluation of two childhood genetic...

A detailed analysis of the constitutional chromosomal changes in two pediatric patients was performed using high resolution genetic analysis techniques, microarray comparative genomic hybridization (array CGH) and multiplex ligation-dependent probe amplification (MLPA) as well as FISH. The aim was to come to a more precise characterization of the genotype/phenotype relationship. Case 1 was a girl of 25 months, showing areas of hypopigmentation along the lines of Blaschko and no other developmental abnormality. She carried a ring chromosome 19 which we found not to have resulted in loss of subtelomeric sequences, ruling out the possibility that a small subtelomeric loss was causally related to this patient's phenotype. Case 2 was a 9-year-old girl with facial anomalies and mild growth and mental retardation carrying an unidentified addition on chromosome 2p. We found that the addition was duplicated 2q35-q37.3 and that the addition was not accompanied by loss of 2pter or any other chromosomal region. Together with literature data, we hypothesize that pediatric patients with 'pure' trisomy 2q including bands 2q35-q37.1 may have a moderate clinical phenotype as opposed to patients with duplications proximal to 2q33 or patients with duplications 2q3 with accompanying distal deletion. These two examples illustrate the additional value of new, high resolution genetic analysis techniques for a better characterization of the genotype/phenotype relationship in childhood chromosomal disorders.