Résumé :
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In the families with a reported case of dystrophinopathy, pedigree analysis with measurement of blood creatine phosphokinase (CK) are commonly used for genetic risk assessment of relatives. Several affected cases in the same family across generations or the presence of female relatives with elevated CK levels are usually indicative of a familial case. In some instances this approach can lead to misinterpretations and we present here three situations where genetic testing has been crucial to clarify genetic status for family members. Case 1: deceased sporadic case of Duchenne Muscular Dystrophy (DMD) without samples available. In this family, the maternal aunt of the proband was found to have high CK level (three independent dosages, in the absence of known confusing factors). Thus, it was predictive of a familial transmission of a dystrophin gene mutation making the proband's mother an obligatory carrier. Haplotype analysis showed that both daughters had inherited the same X maternal chromosome. A deleterious mutation was identified in the proband's mother DNA. Unexpectedly this mutation was not detected in the DNA of the aunt. The cause of the elevated CK in this woman reminds to be elucidated. Case 2 : Occurrence of a merosine negative congenital muscular dystrophy (CMD1A) in a family with two first-degree cousins affected by DMD. Because of the familial history, DMD was the first suggested diagnosis. Genetic testing has allowed to rule out this hypothesis and to identify mutations in the LAMA2 gene. Case 3 : Independent DMD mutational events in a same pedigree. In this apparent familial case of DMD, two second-degree cousins were found to carry distinct mutations of the dystrophin gene. Our data emphasize the usefulness of exhaustive familial analyses and the need to genotype all affected individuals and potential carriers in families with a dystrophinopathy.
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