Validation of a "new" short tandem repeat (STR) fluorescent multiplex system and report of population genetic data.

The Humantype Chimera PCR Amplification Kit contains 12 polymorphic loci (ACTBP2 (= SE33), D18S51, D4S2366, D6S474, D8S1132, D12S391, D2S1360, D3S1744, D5S2500, D7S1517, D10S2325, D21S2055), of which the latter 10 loci have not been used extensively for human identity testing. The sex determinant locus amelogenin is also included in the kit. Amplification was successful on a variety of thermal cyclers and the amplicons could be analyzed on both the ABI PRISM 310 and 3100 Genetic Analyzers.

Evidence for a modifying pathway in SMA discordant families: reduced SMN level decreases the amount of its interacting partners and Htra2-beta1.

Proximal spinal muscular atrophy (SMA) is a neuromuscular disorder caused by homozygous mutations of the SMN1 gene. SMN1 interacts with multiple proteins with functions in snRNP biogenesis, pre-mRNA splicing and presumably neural transport. SMN2, a nearly identical copy of SMN1, produces predominantly exon 7-skipped transcripts, whereas SMN1 mainly produces full-length transcripts.

Exclusion of Htra2-beta1, an up-regulator of full-length SMN2 transcript, as a modifying gene for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by homozygous mutations of the survival motor neuron gene 1 (SMN1). In rare cases sibs with identical 5q13-homologs and identical SMN1 mutations can show variable phenotypes from unaffected to affected, suggesting the influence of modifying genes. SMN is part of an 800 kDa macromolecular complex that plays an essential role in snRNP biogenesis and pre-mRNA splicing.

An essential SMN interacting protein (SIP1) is not involved in the phenotypic variability of spinal muscular atrophy (SMA).

The survival motor neuron (SMN) protein and the SMN interacting protein 1 (SIP1) are part of a 300 kD protein complex with a crucial role in snRNP biogenesis and pre-mRNA splicing. Both proteins are colocalised in nuclear structures called gems and in the cytoplasm. Approximately 96% of patients with autosomal recessive spinal muscular atrophy (SMA) show mutations in the SMN1 gene, while about 4% fail to show any mutation, despite a typical SMA phenotype.