¹Servei de Genètica, Hospital de Sant Pau, Barcelona, Spain

²Division of Molecular Genetics, Institute of Biomedical and Life Sciences, University of Glasgow, UK

³Servei de Neurología, Hospital de la Vall d'Hebrón, Barcelona, Spain

Correspondence to: Loreto Martorell , Servei de Genètica, Hospital de Sant Pau, Pare Claret 167, 08025-Barcelona, Spain. Tel: +34 3 2919194; Fax: +34 3 2919494; E-mail: genm@santpau.es

The genetic basis of myotonic dystrophy type 1 (DM1) is the expansion of a CTG repeat in the 3' untranslated region of DM1PK. Once into the disease range, the repeat becomes highly unstable and is biased toward expansion in both somatic and germline tissues. Intergenerational differences usually reveal an increase in allele length, concordant with the clinical anticipation characteristic of DM1, but there have also been cases with intergenerational contractions of the repeat length, accompanied by apparent anticipation. In order to gain a better understanding of this intergenerational behaviour, we have obtained semen samples from six DM males and used single molecule analyses to compare the allele distributions present in their sperm and blood with those of their offspring. We have confirmed that the male germline mutational pathway is distinct from that of the soma, but the extent of variation is highly variable from one individual to another and not obviously correlated with progenitor allele length. Nonetheless, in all cases the alleles present in the father's sperm overlap with those observed in their offspring. These data also provide further indications that the interpretation of intergenerational transmissions by standard analyses is frequently compromised by the masking of germline differences by age-dependent somatic expansion in the parent. European Journal of Human Genetics (2000) 8, 423-430.

germline; CTG repeat; instability; mosaicism; contraction