ABSTRACT
Myotonic dystrophy type 1 (DM1) is a dominant multisystemic disorder caused by expansion of a trinucleotide repeat in a non-coding region of DMPK. Prenatal diagnosis (PND) is available; however, the decision to terminate affected pregnancies is difficult as the extent of disability is hard to predict from the size of the expansion. In preimplantation genetic diagnosis (PGD) genetic analysis is carried out before the establishment of pregnancy. This paper reviews the largest number of cycles of PGD for DM1 in the UK indicating that PGD is a practical option for affected couples.
Subject(s)
Genetic Testing , Myotonic Dystrophy/diagnosis , Myotonic Dystrophy/genetics , Preimplantation Diagnosis , Protein Serine-Threonine Kinases/genetics , Female , Fertilization in Vitro , Humans , Male , Myotonin-Protein Kinase , Polymerase Chain Reaction , Trinucleotide Repeats , United KingdomABSTRACT
OBJECTIVE: To report two cases of preimplantation genetic diagnosis (PGD) for myotonic dystrophy type I (DM1) where cross-over between the DMPK locus and a linked polymorphic marker APOC2 was detected. METHODS: Embryos from in vitro fertilisation (IVF) were biopsied at day 3 of development and single blastomeres collected. Diagnosis was performed by duplex or triplex fluorescent-polymerase chain reaction (F-PCR) to amplify DMPK and APOC2 loci, or DMPK with APOC2 and D19S112 polymorphic markers. RESULTS: A total of 22 oocytes were retrieved from the two patients, 20 were inseminated of which 15 fertilized (75%) and were suitable for biopsy on day 3. A diagnosis was obtained for 12 embryos (80%) and was confirmed in all un-transferred embryos. Crossover between DM1 and APOC2 was detected in two embryos from the two different couples. Transfer of two embryos took place in both cases resulting in two pregnancies. Each couple have had a healthy baby. CONCLUSION: The above cases highlight the importance of using more than one linked polymorphic marker in PGD-PCR protocols and emphasize the danger of using APOC2 as the sole marker to identify the DM1 mutation.
Subject(s)
Apolipoprotein C-II/genetics , Crossing Over, Genetic/genetics , Genetic Testing , Myotonic Dystrophy/diagnosis , Preimplantation Diagnosis/methods , Protein Serine-Threonine Kinases/genetics , Adult , Biopsy , Female , Fertilization in Vitro , Genetic Linkage , Genetic Markers/genetics , Humans , Male , Myotonic Dystrophy/genetics , Myotonin-Protein Kinase , Oocytes/chemistry , Oocytes/pathology , Polymerase Chain Reaction , PregnancyABSTRACT
OBJECTIVES: The complete cytogenetic investigation of human oocytes and the corresponding first polar bodies (PBs) derived from an 18-year old female cancer patient. METHODS: A whole-genome amplification method combined with comparative genomic hybridisation (CGH) was employed for the analysis of 14 oocytes and their corresponding first PBs. RESULTS: Chromosome abnormalities were detected in two oocyte-PB complexes. One oocyte had lost X-chromosome material (23,X,-Xcht), while its corresponding first PB showed the reciprocal gain (23,X,+Xcht). Double aneuploidy involving loss of chromatids for chromosomes X and 21 was identified in another first PB (23,X,-21cht,-Xcht). Aneuploidy was attributed to unbalanced pre-division of chromatids at meiosis I. CONCLUSIONS: Meiotic errors in chromosome segregation can occur even in oocytes derived from young women, confirming the existence of age-independent factors contributing to aneuploidy. Such factors are of relevance to fertility, miscarriage and preimplantation aneuploidy screening for the purposes of increasing IVF success rates. The reliability of CGH in examining the whole chromosome complement of a single cell and of being able to detect chromatid anomalies is confirmed by this study.
