Davor Begović

Molecular analysis and electromyoneurographic abnormalities in Croatian children with proximal spinal muscular atrophies

Abstract Childhood onset proximal spinal muscular atrophy presents with considerable clinical variability. This study included 14 Croatian children aged 11 days to 8 years with spinal muscular atrophy types I-III verified clinically and electromyoneurographically. DNA of affected children was screened for deletions of exons 7 and 8 of the survival motor neuron gene and for deletion of exon 5 of the neuronal apoptosis inhibitor protein gene. Motor nerve conduction velocity and compound muscle action potential amplitude were decreased in children with spinal muscular atrophy type I and II. Deletions of exons 7 and 8 of the survival motor neuron gene and of exon 5 of the neuronal apoptosis inhibitor protein gene in children with spinal muscular atrophy type I-II suggested existence of more genetic abnormalities as compared to type III. A decrease in compound muscle action potential amplitude and motor nerve conduction velocity in children with spinal muscular atrophy correlated with the disease severity, probably as a result of axonal degeneration. Phenotypic severity in children onset spinal muscular atrophy is directly correlated with the extent of survival motor neuron and neuronal apoptosis inhibitor protein exon deletions.

Application of microsatellite loci on the chromosome X for rapid prenatal detection of the chromosome X numerical abnormalities.

Aim To determine the value of short-tandem repeat markers on the chromosome X (X-STR) for prenatal diagnostics of the chromosome X numerical disorders. Methods We investigated the genetic variability of 5 X-markers (DXS9895, DXS6810, DXS6803, GATA172D05, and HPRTB) in 183 healthy Croatian individuals (90 men and 93 women). We also tested 13 patients with X chromosome disorders (Turner syndrome – 6 cases; Klinefelter syndrome – 5 cases, and Triple X syndrome – 2 cases). The analysis was performed using polymerase chain reaction amplification with specific primers and electrophoresis on a polyacrylamide gel. The study was performed in 2010. Results Our sample showed no significant differences in allelic frequencies of the investigated X-markers from other European populations. A set of 5 X-STR markers was sufficiently informative for a successful determination of the chromosome X numerical abnormalities. Conclusion Since no false positive or negative results were observed, diagnostic value of the investigated X-STR loci for prenatal detection of chromosome X numerical disorders was confirmed. Our study represents an important step toward an improved prenatal diagnostics in Croatia.