A father and son with mental retardation, a characteristic face, inv(12), and insertion trisomy 12p12.3-p11.2

A male patient with mental retardation (MR) and mild facial features was shown by high-resolution G-banding to have pericentric inversion of chromosome 12 with an unknown segment inserted into the long arm of the inverted chromosome [46,XY,inv(12)(pter-->p11.2::q14.1-->p11.2::?::q14.1-->qter)]. Both the inverted chromosome 12 and clinical manifestations were transmitted to his son. Karyotypes of the propositus' parents were normal. Studies with fluorescence in situ hybridization (FISH) in both the propositus and his son revealed that the extra segment was derived from 12p. Further FISH mapping and the genome-wide copy number detection by GeneChip Mapping 100K Array showed that an 11-Mb segment of 12p between two BAC clones, RP11-22H10 and RP11-977P2, was inserted at one of the reunion points in the long arm of the inv(12) chromosome. Analysis of parent-child transmissions of duplicated alleles using microsatellite markers defined the maternal origin of the chromosomal anomaly in the propositus and suggested a mechanism of its formation through a sister-chromatid rearrangement (SCR), that is, mismatched pairing and unequal crossover between sister chromatids as well as three break rearrangements including a U type rearrangement. Karyotypes of the propositus and his son were thus inv(12)(pter-->p11.22::q14.1-->p12.3::q14.1-->qter). This is the first report of "pure" proximal 12p-trisomy including p12.3-p11.22 region.