A family observation of primary dysferlinopathy, an autosomal dominant genetic disorder

Until now, dysferlin deficiencies reported in human pathology have all been inherited in the autosomal recessive mode. A few heterozygous individuals have been reported with slightly elevated CPKEnzyme contenue dans les cellules musculaires, qui est libérée dans le sang en cas d’atteinte musculaire. blood levels. Australian and British researchers found a large family with autosomal dominantEn génétique, c’est la caractéristique d’un individu qui n’a besoin que d’un seul exemplaire d’un certain gène (allèle) pour s’exprimer. Cet exemplaire unique peut venir du père ou de la mère. inheritance.

• There was no particular family consanguinity to explain possible pseudodominance.
• Genetic analysis found only one pathogenic variant c.6207del p. (Tyr2070Metfs*4) despite an extensive search for a second variant, including whole-genome sequencing.
• Depending on the patient, the picture consisted of a chronic elevation of CPK or a slowly progressive proximal deficit of late onset.

Such an observation, if confirmed by other work, could make genetic counseling more difficult in families with dysferlinopathy.

Identification of a novel heterozygous DYSF variant in a large family with a dominantly-inherited dysferlinopathy. Folland C, Johnsen R, Botero Gomez A, et al. Neuropathol Appl Neurobiol. 2022 Aug 12:e12846.