A major imprinted gene involved in hydatidiform mole is not located in 2q31.2-qter or 5q34-qter

INTRODUCTION: Hydatidiform mole is an abnormal human pregnancy, characterised by absent or abnormal embryonic differentiation, vesicular chorionic villi and trophoblastic hyperplasia. Although the mole phenotype has hereto not been correlated to mutations in the molar genome, the aetiology for hydatidiform moles clearly is genetic: Most molar genomes analysed either have had a relative excess of paternal genome sets relative to maternal genome sets, or a global error in maternally imprinted genes, giving them a "paternal pattern". However it remains yet to be specified which gene(s) in the molar genome actually causes the molar phenotype when present in a state of "paternal excess" or "maternal deficiency". MATERIAL AND METHODS: A molar pregnancy in a woman with a balanced translocation (t(2;5) was subjected to histopathological evaluation and genetic analyses of ploidy and parental origin of the genome. RESULTS: Morphology: Partial hydatidiform mole. Karyotyping of metaphase chromosomes: 69,XXY,der(5)t(2;5)(q23;q33)mat. SNP array analysis mapped the breakpoints to 2q31.2 (genome position 179Mb) and 5q34 (genome position 165Mb). DNA microsatellite marker analysis showed that for the regions not involved in the translocation, the conceptus had two paternal and one maternal allele(s). Telomeric to the breakpoint on chromosome 2, the mole had two paternal and two maternal alleles and telomeric to the breakpoint on chromosome 5 the mole had paternal alleles, exclusively. CONCLUSIONS: If the molar phenotype is caused by paternal excess of one gene, only, it is unlikely that this gene is located telomeric to genome position 179Mb on chromosome 2. And similarly, if the phenotype complete mole is caused by the presence of exclusively paternally imprinted alleles of one gene, this gene is not located telomeric to genome position 165Mb on chromosome 5.