Paternal inheritance or different mutations in maternally related patients occur in about 3% of Duchenne familial cases.
Duchenne dystrophy (DMD) is an X-linked lethal condition which affects 1 in 3,500 boys. The DMD gene is deleted in about 60-65% of patients while in the remaining 35-40% the condition is caused by point mutations, small insertions, or duplications. We have ascertained 967 DMD families (680 isolated and 287 familial cases). Screening for deletions showed a molecular deletion in 383 among 615 (62.3%) analyzed cases. However, 10 families were unusual: In 7 of them, 2 or more DMD patients were related through paternal lines while in 3 others, affected boys related through maternal lines carried different mutations or originated through independent new mutation events. The finding of 10 atypical genealogies, which represent about 1% of the sample (10/967) or about 3% of familial cases (10/287) is higher than we would expect by chance. Even so, it is an underestimate because screening of mutations in all the affected DMD relatives from each genealogy is not done in many of the familial cases. It suggests that other mechanisms (such as transposon-like elements, for example) could be responsible for a higher genomic instability leading to novel mutations as reported previously by us and others in DMD and in other genetic disorders such as hemophilia and inherited peripheral neuropathies. On the other hand, it shows the importance of testing all affected patients within each genealogy to prevent possible mistakes in carrier detection, genetic counseling, and prenatal diagnosis.
Departamento de Biologia, Instituto de Biociências, Universidade de São Paulo, Brazil. mayazatz@usp.br
M
M
Zatz
D
D
Sumita
S
S
Campiotto
M
M
Canovas
A
A
Cerqueira
M
M
Vainzof
M R
MR
Passos-Bueno
D002648:Child; D002675:Child, Preschool; D003402:Creatine Kinase / Q000097:blood; D004251:DNA Transposable Elements / Q000235:genetics; D016189:Dystrophin / Q000235:genetics*; D005220:Fathers; D008040:Genetic Linkage; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D009035:Mothers; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D009679:Nuclear Family; D010375:Pedigree; D017384:Sequence Deletion; D014960:X Chromosome / Q000235:genetics*
D004251:DNA Transposable Elements; D016189:Dystrophin; D003402:Creatine Kinase