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Lafora progressive myoclonus epilepsy (LD; OMIM 254780) is an autosomal-recessive disorder caused in ∼80% of patients by mutations in the EMP2A gene, which is located on chromosome 6q24 (1-3). The EPM2A gene is composed of four exons that encode a dual-specificity phosphatase (laforin) (2,3). Recently, mutations in the gene NHLRC1 (also called EPM2B), which is a putative E3 ubiquitin ligase encoding malin, also have been shown to be responsible for LD (4).LD classically starts during early adolescence in an otherwise neurologically normal individual as myoclonic and occipital lobe seizures followed by rapidly progressive neurologic deterioration that leads to death between ages 17 and 24 years (1). A recent study (5), however, gave evidence of a genotype-phenotype relation in LD with two main subsyndromes: (a) classic LD associated mainly with mutations in exon 4, and (b) atypical LD with childhoodonset learning disorder followed by epilepsy and neurologic deterioration, associated mainly with mutations in exon 1.We report on a 17-year-old right-handed boy with LD from southern Italy, who had a normal birth and early development milestones. His father and mother were unrelated and healthy. Around the age of 5 years, he was noticed to be less bright than his older brothers. He had learning problems and educational difficulties, as evidenced by poor school performance, poor memory and calculating abilities, with repetition of school years. In the ensuing years, an insidious progressing intellectual deterioration

The isolation and analysis of nucleated fetal cells (NFCs) from maternal blood may represent a new approach to noninvasive prenatal diagnosis. Although promising, these techniques require highly accurate separation of NFCs from nucleated cells of maternal origin; the two major problems limiting these techniques are the relative rarity of fetal cells in maternal blood and the need to establish their fetal origin. We now report a novel procedure that has allowed accurate separation of NFCs from maternal cells. The technique reported involves direct micromanipulator isolation of histochemically identified hemoglobin F-positive nucleated cells to obtain fetal nucleated red blood cells (FNRBCs) of high yield and purity. Using this technique, followed by cell-by-cell multicolor fluorescence in situ hybridization (FISH) analysis of purified FNRBCs, we were able to detect some of the most common human aneuploidies (including Down syndrome, Klinefelter syndrome, and trisomy 13) in 33 pregnant women referred for amniocentesis. The procedure used, which can be completed in <72 hrs, produced complete concordance with the results of amniocentesis. We also confirm findings of prior studies suggesting that the number of FNRBCs in maternal circulation is remarkably higher in abnormal pregnancies than in normal pregnancies, especially in women carrying a fetus with trisomy 21.