A Recombinant Abnormal Gamete Resulting from a Balanced Pericentric Inversion of Chromosome 4: an Affected Boy with Wolf-Hirschhorn Phenotypes

Wolf-Hirschhorn syndrome is a genetic disorder that characterized by distinct craniofacial dysmorphology, pre- and postnatal growth deficiency, intellectual disability and seizures. During meiosis, chromosome 4 homologue with a pericnetric inversion can give rise to two recombinant chromosome 4; namely partial monosomy 4p/partial trisomy 4q or partial monosomy 4q/partial trisomy 4p, respectively. Here, we report a one-year-old Iranian boy presented with distinct clinical features of Wolf-Hirschhorn syndrome. G banded chromosome analysis of the proband cultured lymphocytes revealed 46 chromosomes in all cells with a chromosome 4 with partial monosomy 4p and partial Trisomy 4q. Parental chromosome analysis was done to assess whether this abnormal chromosome 4 is inherited or de novo. Karyotyping result of his father was designated as 46,XY,inv(4)(p16.3q34.3). Further characterization of breakpoints with array-CGH confirmed the karyotyping result and revealed a deletion/duplication syndrome, about 50kb in the size, with 4p partial monosomy and 4q partial Trisomy. Final karyotype nomenclature was: 46,XY,rec(4)dup(4q)inv(4)(p16.3q34.3)pat. To date few cases of rec(4) with the different break point have been published. The phenotype variability and the viability of the recombinant offspring depend on the size of the deletion/duplication segments. Our result highlights that the parental chromosomal rearrangements can also contributes to the pathogenesis of such a popular chromosomal microdeletion syndrome and underscores the need to analyze parental karyotype for precise genetic counseling.

کلیدواژه ها:

Wolf-Hirschhorn ، pericentric inversion ، recombinant chromosome ، rec(4) ، Array CGH ، partial monosomy ، partial trisomy