Molecular cytogenetic characterization of a 4p15.1-pter duplication and a 4q35.1-qter deletion in a recombinant of chromosome 4 pericentric inversion.

To date, 10 cases of recombinant of chromosome 4 pericentric inversion involving sub-bands p14p15 and q35 have been described. We report on the first case analyzed using array-CGH in a female infant presenting psychomotor and growth retardation, facial anomalies, axial hypotonia, short neck, wide spaced nipples and cardiac defects. Conventional karyotype associated to FISH revealed a recombinant chromosome 4 with partial 4p duplication and 4q deletion derived from a paternal pericentric inversion. Array-CGH allowed us to precise rec4 breakpoints: the proposita carried a small 4.82-4.97 Mb 4q35.1 terminal deletion and a large 35.3-36.7 Mb 4p15.1 terminal duplication. Duplications of the distal 2/3 of short arm of chromosome 4 give rise to recognizable craniofacial features but no specific visceral malformation. A contrario small terminal 4q deletions are associated with cardiac defects. This case and review of literature suggest that two genes ArgBP2 and PDLIM3, located at 4q35.1 and both involved in cardiac and muscle development, could be responsible for cardiac defects observed in terminal 4q35.1 deletions. (c) 2009 Wiley-Liss, Inc.