Mutation information:
NumberExon/IntronNucleotide change Protein changeLocation Mutation typeConsequencesPhenotype InheritanceReference
1223c.434T>Cp.Met145ThrDIS1MissenseN→P/O (81); pLOFPEFS+(FS&TLE)Familial(Maternal,FS),P=5/5Mantegazza M.2005,Colosimo E.2007

Functional information:
NumberNucleotide changeProtein changeLocationPhenotypeFunctional defect type Details of the major biophysical abnormalities.Reference
1c.434T>Cp.Met145Thr(M145T)DIS1PEFS+ fpLOF 60% reduction of current density, 10-mV positive (hypoexcitable) shift of activation curve.Mantegazza M.2005

Inheritance information:
NumberNucleotide changeProtein changeMutation type Proband's phenotype1st transmitter's phenotype Mosaic Affected generationsPenetranceReference
18c.434T>Cp.Met145Thr(DIS1)MissensePEFS+FS(Maternal) 5/5Colosimo E.2007

[c.434T>C] Clinical description

The family contained 35 individuals spread over four generations. A total of 13 living members had FS ( the age at onset of FS ranged from 5 months to 4 years, with a mean age of 18 months).  Three individuals (III-3, IV-3, and IV-5; aged 38, 17, and 22 years, respectively) at the age of 10, 13, and 11 years, respectively, developed afebrile simple partial seizures of temporal lobe origin with vegetative or experiential phenomena. Very rare partial complex seizures or nocturnal secondary generalized tonic-clonic seizures also occurred in all of them. Other ten  affected individuals had only simple FS. The neurologic and psychiatric status of all 13 affected subjects was normal. The electroencephalogram analysis showed interictal anteromesiotemporal epileptiform abnormalities that were seen in all three patients with afebrile temporal lobe seizures. One patient (IV-3) had one typical seizure recorded with onset in the right midinferomesial temporal region. Two patients (III-3 and IV-3) with afebrile seizures had MRI evidence of unilateral mesial temporal sclerosis (MTS), which consisted of an abnormal high signal intensity detected on fluid-attenuated inversion recovery (FLAIR) and T2-weighted images ipsilateral with the electroencephalogram abnormalities. Antiepileptic medication always allowed good control of afebrile seizures. Thus, the pedigree analysis supports a highly ( 90%) penetrant AD trait of simple FS in this family. Among the 13 affected family members, three patients developed subsequent afebrile seizures, whose electroclinical features were consistent with mesial temporal lobe epilepsy (MTLE). This phenotype resembles the phenotype that is encountered in families with AD FS, in which some individuals may develop later MTLE associated with MTS, whereas it differs from that reported in generalized epilepsy with FS plus (GEFS+) families.(Mantegazza M, et al. Proc Natl Acad Sci U S A. 2005 Dec 13; 102(50): 18177-82. [16326807])