First description of germline mosaicism in familial hypertrophic cardiomyopathy

doi:10.1136/jmg.37.2.132

Journal of Medical Genetics 2000;37:132-134; doi:10.1136/jmg.37.2.132

J Med Genet 2000;37:132-134 ( February )

Short report

First description of germline mosaicism in familial hypertrophic cardiomyopathy Jean-François Forissier^a, Pascale Richard^b, Sylvain Briault^c, Céline Ledeuil^b, Olivier Dubourg^f, Bernard Charbonnier^a, Lucie Carrier^d, Claude Moraine^c, Gisèle Bonne^d, Michel Komajda^e, Ketty Schwartz^d, Bernard Hainque^b

^a Service de Cardiologie, Hôpital Trousseau, 37044 Tours Cedex, France, ^b Service de Biochimie B, Hôpital de la Salpêtrière, 47 Bld de l'Hôpital, 75651 Paris Cedex 13, France, ^c Service de Génétique, CHU Bretonneau, Tours, France, ^d INSERM U 523, Hôpital de la Salpêtrière, Paris, France, ^e Service de Cardiologie, Hôpital de la Salpêtrière, Paris, France, ^f Service de Cardiologie, Hôpital Ambroise Paré, Boulogne, France

Correspondence to: Dr Hainque

Revised version received 28 July 1999; Accepted for publication 23 September 1999

Familial hypertrophic cardiomyopathy is a genetically and phenotypically heterogeneous disease caused by mutations in sevensarcomeric protein genes. It is known to be transmitted as anautosomal dominant trait with rare de novomutations.
A French family in which two members are affected by hypertrophic cardiomyopathy was clinically screened with electrocardiographyand echocardiography. Genetic analyses were performed on leucocyteDNA by haplotype analysis with microsatellite markers at the MYH7locus and mutation screening by single strand conformation polymorphismanalysis. Two subjects exhibited severe hypertrophic cardiomyopathy.A mutation in the MYH7 gene was found in exon 14 (Arg453Cys).The two affected patients were carriers of the mutation, whichwas not found in the circulating lymphocytes of their parents.Haplotype analysis at the MYH7 locus with two intragenic microsatellitemarkers (MYOI and MYOII) and the absence of the mutation in thefather's sperm DNA suggested that the mutation had been inheritedfrom the mother. However, it was not found in either her fibroblastsorhair.
This is the first description of germline mosaicism shown by molecular genetic analysis in an autosomal dominant disorderand more especially in hypertrophic cardiomyopathy. This mosaicismhad been inherited from the mother but did not affect her somaticcells. Such a phenomenon might account for some de novo mutationsin familial hypertrophiccardiomyopathy.

Keywords: hypertrophic cardiomyopathy; germline mosaicism; $beta$ myosin heavy chain; genetics

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