Cytogenetic And Molecular Analysis In A Proband And His Son With Mental Retardation

A male proband with mental retardation and mild facial features has been clinically investigated since 1981 and high resolution chromosome G-banding show that he carries an apparently pericentric inversion 46, XY, inv(12)(pllql4) and a cytogenetically unrecognizable extra chromosomal material inserted into 12q[46, XY, inv(12)(pter→ p11.2::q14.1→p11.2::?::q14.1→qter)]. Both of the karyotype and phenotype were steadfastly transmitted to his son. To identify the extra chromosomal material and the breakpoints, delineate the genotype/ karyotype-phenotype correlation for this unknown syndrome and find out the pathogenesis of mental retardation, the chromosomal painting for the breakpoints was carried out using fluorescence in situ hybridization (FISH) in both proband and his son, which implied that the extra segment was derived from 12p. Further FISH analysis mapped 12p breakpoint or the proximal end of 12p duplication to a 124kb (chr12: 28755133-28878898) region on 12p11.22, 12q breakpoint to a 70kb (chr12: 58510500-58580370) on 12q14.1 and the distal end of 12p duplication to a 29kb (chr12: 17695757-17725491) on 12p12.31, resulting in a HMb(chr12: 17695757-28878898) of 12p duplication [dup(12) (p12.31p11.22)], which was shown to insert reversely at one of the reunion points in the long arm of the inv(12) chromosome by double-color FISH.We further performed the genome-wide copy number detection in both the proband and his son by GeneChip Mapping 100K Array with 116,314 SNPs and a resolution of 0.3-0.5Mb, which showed the proximal end of 12p duplication within a 165kb(chr12: 28724178-28889151) between SNP_A-1716707 and SNP_A-1757551 of XabI array on 12p11.22 and the distal end of 12p duplication within a 232kb (chr12: 17708381-17940493) between SNP_A-1662961 of HindIII array and SNP_A-1662196 of XabI array on 12p12.31, resulting in a 11Mb(chr12: 17708381-28889151) of 12p duplication between SNP_A-1662961 and SNP_A-1757551 (12p12.31-p11.22). The results were co-confirmed with those by FISH. It is the first report to analyze copy number using...