TY - JOUR
T1 - Familial Ohtahara syndrome due to a novel ARX gene mutation
AU - Giordano, L.
AU - Sartori, S.
AU - Russo, S.
AU - Accorsi, P.
AU - Galli, J.
AU - Tiberti, A.
AU - Bettella, E.
AU - Marchi, M.
AU - Vignoli, A.
AU - Darra, F.
AU - Murgia, A.
AU - Bernardina, B. Dalla
PY - 2010/12
Y1 - 2010/12
N2 - Recently, it has been reported that longer expansions of the polyalanine tract of the ARX gene could cause an early infantile encephalopathy with suppression burst pattern and that the length of this repeat region could be related to the severity of the electroclinical picture. We describe the history of two male individuals, born from monozygotic twin sisters, with Ohtahara syndrome (OS) that evolved into West syndrome phenotype and epileptic encephalopathy. In both children, we have found a previously unreported missense mutation in exon 5 of ARX gene (c.1604T>A) resulting in the substitution of a leucine with a glutamine in the aminoacid sequence. The two mothers and the maternal grandmother carry the same mutation which segregates with the disease phenotype in the family. This study confirms that ARX is involved in the pathogenesis of cryptogenic early onset epileptic encephalopathy, such as OS, and suggests that the severity of the electroclinical picture is likely to not exclusively correlate with the extent of expansions of the polyalanine tracts, but rather with the functional effect of different pathogenetic mutations.
AB - Recently, it has been reported that longer expansions of the polyalanine tract of the ARX gene could cause an early infantile encephalopathy with suppression burst pattern and that the length of this repeat region could be related to the severity of the electroclinical picture. We describe the history of two male individuals, born from monozygotic twin sisters, with Ohtahara syndrome (OS) that evolved into West syndrome phenotype and epileptic encephalopathy. In both children, we have found a previously unreported missense mutation in exon 5 of ARX gene (c.1604T>A) resulting in the substitution of a leucine with a glutamine in the aminoacid sequence. The two mothers and the maternal grandmother carry the same mutation which segregates with the disease phenotype in the family. This study confirms that ARX is involved in the pathogenesis of cryptogenic early onset epileptic encephalopathy, such as OS, and suggests that the severity of the electroclinical picture is likely to not exclusively correlate with the extent of expansions of the polyalanine tracts, but rather with the functional effect of different pathogenetic mutations.
KW - ARX gene
KW - EEG
KW - Gene expression studies
KW - Infantile spasms
KW - Neonatal seizure
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U2 - 10.1002/ajmg.a.33701
DO - 10.1002/ajmg.a.33701
M3 - Article
C2 - 21108397
AN - SCOPUS:78649647282
VL - 152 A
SP - 3133
EP - 3137
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 12
ER -