RESUMEN
The facilitative glucose transporter-1 (GLUT1) deficiency or de Vivo syndrome is a rare neuropediatric disorder characterized by drug-resistant epilepsy, acquired microcephaly, delayed psychomotor development, intermittent ataxia, and other paroxysmal neurological disorders due to the presence of dominant mutations in the SLC2A1 gene. Alternating hemiplegia of childhood (AHC) is another rare neuropediatric disorder characterized by episodes of hemiplegia developing during the first 1.5 years of life. Before the recent finding of the gene ATP1A3 as the major cause of AHC, a heterozygous missense mutation in the SLC2A1 gene encoding GLUT1 was described in one child with atypical AHC, suggesting some clinical overlap between AHC and GLUT1 deficiency syndrome (GLUT1DS1). Half of patients with symptoms evocative of GLUT1DS1 with hypoglycorrhachia and up to 25 % of patients with AHC remain molecularly undiagnosed. We investigated whether mutations in SLC2A3 encoding GLUT3, another glucose transporter predominant in the neuronal cell, may account the case of a cohort of 75 SLC2A1 negative GLUTDS1-like patients and seven patients with AHC who were negative for ATP1A3 and SLC2A1 mutations. Automated Sanger sequencing and qPCR analyses failed to detect any mutation of SLC2A3 in the patients analyzed, excluding this gene as frequently mutated in patients with GLUT1DS1 like or AHC.
RESUMEN
Walker Warburg syndrome (WWS) is the most severe of a group of multiple congenital disorders known as lissencephaly type II ( LIS Type II) associated with congenital muscular dystrophy and eye abnormalities. The POMT1 gene is the most frequently affected found in 20% of patients with WWS. We describe five fetuses with WWS in three non-related families carrying a same mutation in the POMT1 gene. All fetuses presented with tetra ventricular hydrocephaly, and arachnoidal neuroglial ectopia and cortical dysplasia characteristic of LIS type II. We performed sequencing of the POMT1 gene on fetal DNA. The five fetuses were found to share an insertion of an inversed Alu repeated DNA element within exon 3 of the POMT1 gene, all at the heterozygous state except one at the homozygous state. This mutation was associated with a common transition c.2203 C > T (p.Arg735Cys) in exon 20 on the same allele and similar intragenic haplotype, suggesting that the three families could be related or indicating a possible founder effect in France. Insertions of Alu sequences, which are rarely found in coding regions, have occasionally been reported to cause other genetic diseases. However, this is the first report of a retrotransposon insertion in the POMT1 gene associated with WWS.