Benign familial infantile convulsions: mapping of a novel locus on chromosome 2q24 and evidence for genetic heterogeneity

Abstract

In 1997, a locus for benign familial infantile convulsions (BFIC) was mapped to chromosome 19q. Further data suggested that this locus is not involved in all families with BFIC. In the present report, we studied eight Italian families and mapped a novel BFIC locus within a 0.7-cM interval of chromosome 2q24, between markers D2S399 and D2S2330. A maximum multipoint HLOD score of 6.29 was obtained under the hypothesis of genetic heterogeneity. Furthermore, the clustering of chromosome 2q24-linked families in southern Italy may indicate a recent founder effect. In our series, 40% of the families are linked to neither chromosome 19q or 2q loci, suggesting that at least three loci are involved in BFIC. This finding is consistent with other autosomal dominant idiopathic epilepsies in which different genes were found to be implicated.

Figure 1

Pedigrees and chromosome 2q24 haplotypes in eight Italian families affected with BFIC. Families 1–4 are linked, whereas families 5–8 are unlinked. Blackened symbols indicate affected subjects, and unblackened symbols indicate individuals with no history of seizures. Question marks (?) within genetic symbols indicate undetermined status. Black vertical bars represent segregation of the disease chromosome within linked families. Hatched bars indicate the presence of a potential disease chromosome in absence of parental genotypes. In individual III-1 of family 6, haplotypes (in brackets) were arbitrarily assigned because of the lack of parental information. Families 1, 5, 6, 7, and 8 are, respectively, families 7, 5, 4, 6, and 2 in the Gennaro et al. (1999) report.

Figure 2

Geographical distribution of BFIC families. Linked families are indicated with underlined numbers.