Difficulties of genetic counseling and prenatal diagnosis in a consanguineous couple segregating for the same translocation (14;15) (q11;q13) and at risk for Prader-Willi and Angelman syndromes.
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are associated with a loss of function of imprinted genes in the 15q11-q13 region mostly due to deletions or uniparental disomies (UPD). These anomalies usually occur de novo with a very low recurrence risk. However, in rare cases, familial translocations are observed, giving rise to a high recurrence risk. We report on the difficulties of genetic counseling and prenatal diagnosis in a family segregating for a translocation (14;15)(q11;q13) where two consanguineous parents carry the same familial translocation in this chromosome 15 imprinting region. Both children of the couple inherited a chromosomal anomaly leading to PWS. However, a paternal 15q11-q13 deletion was responsible for PWS in the first child, whereas prenatal diagnosis demonstrated that PWS was associated with a maternal 15q11-q13 UPD in the fetus. This report demonstrates that both conventional and molecular cytogenetic parental analyses have to be performed when a deletion is responsible for PWS or AS in order not to overlook a familial translocation and to insure reliable diagnosis and genetic counseling.
Flori
Elisabeth
E
Service de Cytogénétique, Fédération de Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Elisabeth.Flori@chru-strasbourg.fr
Biancalana
Valérie
V
Girard-Lemaire
Françoise
F
Favre
Romain
R
Flori
Jean
J
Doray
Bérénice
B
Mandel
Jean Louis
JL
D017204:Angelman Syndrome / Q000175:diagnosis / Q000235:genetics*; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D007621:Karyotyping; D008297:Male; D010375:Pedigree; D011218:Prader-Willi Syndrome / Q000175:diagnosis / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D014178:Translocation, Genetic / Q000235:genetics*