Three Rett patients with both MECP2 mutation and 15q11-13 rearrangements.

Autism and Rett syndrome, a severe neurological disorder with autistic behavior, are classified as separate disorders on clinical and etiological ground. Rett syndrome is a monogenic X-linked dominant condition due to de novo mutations in the MECP2 gene, whereas autism is a neurodevelopmental and behavioral disorder with complex genetic basis. Maternally inherited duplications on 15q11-q13 are found in a fraction of autistic children suggesting that an abnormal dosage of gene(s) within this region might cause susceptibility to autism. Now we show that three Rett patients are carriers of both a MECP2 mutation and a 15q11-q13 rearrangement, suggesting that there might be a relationship between autism-related genes and the MECP2 gene.

A new susceptibility locus for migraine with aura in the 15q11-q13 genomic region containing three GABA-A receptor genes.

Migraine is the most common type of chronic episodic headache. Several population-based family studies have suggested a strong genetic predisposition to migraine, especially migraine with aura (MA). Although several susceptibility loci have been identified, none of the numerous studies performed to date have led to the identification of a gene responsible for the more common forms of migraine. GABA-A receptors and their modulator sites seem to be involved in the pathophysiological events that underlie migraine. We report on clinical and molecular data from a total of 10 families with MA, in which MA segregates as an autosomal dominant trait and presents with homogeneous clinical features. After excluding linkage with the known candidate loci, we used a functional candidate approach and genotyped these families with markers from the 15q11-q13 genomic region, which contains the genes encoding GABA-A receptor subunits. Evidence of linkage was obtained with a parametric two-point linkage analysis (maximum LOD score of 5.56 at a recombination fraction of 0.001 for marker GABRB3) and was supported by multipoint analysis (maximum LOD score of 6.54 between markers D15S113 and D15S1019). The critical region spanned 3.6 Mb. These results provide the basis for further investigation of the hypothesized relationship between a GABA-A receptor dysfunction and migraine.

Mutations in the Dof zinc finger genes DAG2 and DAG1 influence with opposite effects the germination of Arabidopsis seeds.

We describe the Arabidopsis gene DAG2 encoding a Dof zinc finger protein and show that it is involved in the control of seed germination. An Arabidopsis mutant line with a T-DNA insertion in DAG2 isolated by reverse genetics produces seeds that are substantially more dependent than the wild type on the physical stimuli-light and cold treatment-that promote germination. Mutant dag2 seeds also are less sensitive to the germination-promotive effect of gibberellins, because a 10-fold higher amount of gibberellins is needed to restore germination when endogenous gibberellin biosynthesis is blocked. The seed germination characteristics of the dag2 mutant are opposite to those of dag1, a knockout mutant of another Dof gene (DAG1) that we showed previously to be involved in the control of seed germination, and are similar to those of plants that overexpress DAG1. The promoter of the DAG2 gene is active specifically in the vascular system of the mother plant but not in the embryo, and segregation analysis indicates that the effect of the dag2 mutation is maternal. Both characteristics are in common with DAG1; additionally, the DAG1 and DAG2 proteins share high sequence homology and an identical zinc finger domain. These data suggest, and the germination phenotype of the double mutant is compatible with, a model whereby the zinc finger proteins DAG1 and DAG2 act on a maternal switch that controls seed germination, possibly by regulating the same gene(s).