Myotonic dystrophy--no evidence for preferential transmission of the mutated allele: a prenatal analysis.
Myotonic dystrophy is the commonest autosomal dominant type of muscular dystrophy in adults. It is one of the trinucleotide repeat expansion disorders, and its severity correlates with the number of CTG repeats in the myotonic dystrophy gene. It has been suggested that myotonic dystrophy exhibits the phenomenon of preferential transmission of the larger mutated alleles that has been described in other trinucleotide repeat disorders. Several authors have reported that the frequency of transmission of the mutated alleles is higher than 50%--a finding that, if true, does not comply with the Mendelian laws of segregation. However, these studies were based on data from the analysis of pedigrees with ascertainment bias. In our study, we determined the frequency of transmission of mutated alleles using data from prenatal molecular studies, which are not subject to ascertainment bias. This is the first study to examine the segregation of the mutated alleles in myotonic dystrophy in pregnancy. Eighty-three fetuses were examined, 30 of 62 mothers (48.38%) and 8 of 21 fathers (38.09%) transmitted the mutated allele, giving an overall transmission rate of 45.78%. We found no evidence of statistically significant deviation of the frequency of transmission of the mutated alleles from the 50% expected in autosomal dominant disorders. This study, unlike previous ones, excludes preferential transmission in myotonic dystrophy, a finding that may be attributable to the lack of correction for ascertainment bias in previous studies and to the use of prenatal data in this study.
Zunz
Eran
E
Department of Medical Genetics, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.
Abeliovich
Dvorah
D
Department of Human Genetics, Hadassah University Hospital, Ein Kerem, Jerusalem, Israel.
Halpern
Gabrielle J
GJ
Department of Medical Genetics, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.
Magal
Nurit
N
Department of Medical Genetics, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.|Felsenstein Medical Research Center, Petah Tikva, Israel.
Shohat
Mordechai
M
Department of Medical Genetics, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.|Felsenstein Medical Research Center, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
D000483:Alleles; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D009223:Myotonic Dystrophy / Q000175:diagnosis / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D011247:Pregnancy; D011296:Prenatal Diagnosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics
C585517:DMPK protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases