Abstracts

Cohen syndrome (MIM 216550) is an autosomal recessive disorder with features of psychomotor retardation, microcephaly, characteristic facial features, hypotonia, joint laxity, progressive retinochoroidal dystrophy, myopia and neutropenia. Characteristic facial features include high-arched or wave-shaped eyelids, a short philtrum, thick hair, and prominent incisors. Clinically homogenous in the Finnish population, non-Finnish patients show considerable variability. Seizures have never been described in Cohen[apos]s syndrome.
The genetic locus for Cohen syndrome was recently mapped to chromosome 8q and truncating mutations in the COH1 gene were identified. In Finnish patients a founder mutation, C1117fsI1124X has been consistently found while other mutations have been associated with the atypical non-Finnish Cohen[apos]s syndrome. One of us (VPU) observed several clinical features of Cohen[apos]s syndrome in Indian patients with cryptogenic epilepsy. A pilot study confirmed eight Cohen-like features in a group of children with cryptogenic epilepsy when compared with controls. This prompted us to study the COH1 gene in such patients., We systematically studied patients with cryptogenic epilepsy and a Cohen-like phenotype for all features of Cohen[apos]s syndrome and included only those with at least 5/8 clinical features that we had found to be significant in our previous study.
We initially screened for all the reported common mutations and later sequenced all 62 exons of the COH1 gene in this cohort of 24 patients. We also collected DNA from age, sex and ethnically matched controls., We found several novel mutations such as Y413X, A829T and G3407R in the COH1 gene in 8 of 24 patients (33%). Interestingly, we did not find any of the earlier reported mutations including the most common mutation, C1117fsI1142X. The commonest mutation Y413X was identified in 4 patients, of which one was a compound heterozygote with the G3407R mutation. These mutations were not observed in any of the 100 controls. The mutations were mostly observed in the heterozygous condition except in one patient who was homozygous for the G3407R mutation. We could not find any clinical differences in the patients with and without mutations. However the patients with mutated COH1 had a significantly higher number of Cohen[apos]s syndome features than those without the mutations., We conclude that novel COH1 mutations are strongly associated with Indian patients of cryptogenic epilepsy with a Cohen [ndash] like phenotype. There is however a possibility of additional mutations in the non-coding regions of the COH1 gene or in other genes.Functional analysis will throw more light on the mechanisms by which these mutations may be causally related to the epilepsy which is a characteristic feature in these patients., (Supported by Research Society, PD Hinduja National Hospital.)