Conditions with No Available Direct Mutation Testing

Although the availability of the sequence information is one of the major conditions in undertaking PGD for Mendelian diseases, it is also possible to perform PGD when no exact mutation is known. One of the examples demonstrating feasibility of the approach may be the most recent report of PGD for autosomal dominant polycystic kidney disease (ADPKD), caused by either PKD1 orPKD2

genes, for which no direct testing is yet available in most of the couples at risk, making linkage analysis the method of choice.

ADPKD is a common genetic disorder present in 1/1000 individuals worldwide, which causes progressive cyst formation and may eventually lead to renal failure by late middle age, requiring renal transplantation or dialysis [12]. The overall health implications of ADPKD are obvious from the fact that approximately 10% of all patients at need for renal transplantation or dialysis have this disease. ADPKD is caused by either PKD1 or PKD2 genes [31-33]. Because of an extremely variable expression and the age of onset, much higher in PKD2, only half of the patients carrying these genes may present with severe clinical manifestation and renal failure, making prenatal diagnosis and pregnancy termination highly controversial. PGD may, therefore, be more attractive for the at-risk couples, because an ADPKD-free pregnancy may be established from the onset,

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