New mutation in TSC1-gene in a sporadic case with initially mild phenotype

Introduction:

Mutation in TSC2-gene is observed in nearly 70% of sporadic cases with tuberous-sclerosis-complex (TSC). We will describe a sporadic case with a new mutation in TSC1-Gen, which initially caused diagnostic difficulties.

Case report:

7th from 7 children from non-consanguin parents with uneventful development in early childhood shows at the age of 4y first Absence-like seizure, with subsequent neurological deterioation with polymorph and multiple daily seizures. Pseudo-Lennox-syndrome was suspected and a therapy with valproate was initiated in another hospital. Brain MRI showed on FLAIR-sequences 2 hyperintensities, left hemisphere high-parietal in the mesio-dorsal white matter and right hemisphere temporal, without any specific classification.

Transfer of the patient to our hospital: 1 white spot on the tight was found in physical examination, 4 more hypomelanotic macules have been found under Wood's light. Neuropsychological testing showed an IQ of 63.

Suspecting the child to have a TSC we re-evaluated the brain scan: pathology compatible with TSC, however, no finding of subependymal nodules.

In gene analyses a new sequence variant in Exon 7 of the TSC1-gene was detected: c.808C>T(p.P196L). As the missense-mutation has not been found neither in TSC-patients nor in controls molecular result was interpreted as an unclassified normal variant. No mutation was detected in parents, suggesting that the mutation of our patient was responsible for here symptoms. Now at the age of 8y our patient shows adenoma sebaceum, a classical cutaneous manifestation – indicating the mutation is pathogenic.

Summary:

At the beginning of the epilepsy brain scan and clinic were not typical for TSC. In genetic analysis of TSC1-gene a new missense-mutation in Exon 7 was found.

Conclusion: The clinical development proves that the new mutation is pathogenic.

new mutation TSC1-gene - sporadic case - sequence variant