General information: The SALSA MLPA
Probemix P061 Lissencephaly is a
research use only (RUO) assay for the detection of deletions or duplications in the
PAFAH1B1,
DCX,
POMT1,
POMGNT1 and
FLNA genes, which is associated with Lissencephaly.
Classical lissencephaly (LIS1), or isolated lissencephaly sequence (ILS), and subcortical band heterotopia (SBH) are neuronal migration disorders associated with severe mental retardation and epilepsy. Abnormalities of the
PAFAH1B1 and
DCX genes are implicated in the majority of patients with these disorders and account for approximately 75% of patients with ILS, whereas mutations of
DCX account for 85% of patients with SBH. Lissencephaly may be associated with other diseases including Miller-Dieker syndrome, and Walker-Warburg syndrome. Duplications of the 17p13 region encompassing
PAFAH1B1 have been reported to result in mild to moderate developmental delay.
This probemix includes probes for the lissencephaly related genes, such as;
PAFAH1B1 (LIS1),
DCX (SBH),
POMT1 (Walker-Warburg syndrome),
POMGNT1 (Muscle-Eye-Brain disease) and
FLNA (periventricular nodular heterotopia, frontometaphyseal dysplasia and otopalatodigital syndrome).
The
PAFAH1B1 gene (11 exons), spans ~92 kb of genomic DNA and is located on chromosome 17p13.3, ~2.5 Mb from the p-telomere.
The
DCX gene (7 exons), spans ~118 kb of genomic DNA and is located on chromosome Xq23, ~111 Mb from the p-telomere.
The
POMT1 gene (20 exons), spans ~21 kb of genomic DNA and is located on chromosome 9q34.13, ~131.5 Mb from the p-telomere.
The
POMGNT1 gene (22 exons), spans ~10 kb of genomic DNA and is located on chromosome 1p34.1, ~46 Mb from the p-telomere.
The
FLNA gene (48 exons), spans ~26 kb of genomic DNA and is located on chromosome Xq28, ~154 Mb from the p-telomere.
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK5189.
Probemix content: The SALSA MLPA Probemix P061-D2 Lissencephaly contains 54 MLPA probes with amplification products between 124 and 503 nucleotides (nt). This includes: one probe for each exon of the
PAFAH1B1 gene, two probes are included for exon 1 and 2; eight probes flanking
PAFAH1B1 are included, five upstream and three downstream; eight probes for all exons of the
DCX gene with the exception of exon 1, two probes are included for exons 2 and 3; four probes for the
POMT1 gene; four probes for the
POMGNT1 gene; six probes for the
FLNA gene. In addition, eleven reference probes are included in P061-D2, that detects several chromosomal autosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes are available online (
www.mlpa.com).
This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity fragments (Q-fragments), two DNA Denaturation fragments (D-fragments), one Benchmark fragment, and one chromosome X and one chromosome Y-specific fragment. More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at
www.mlpa.com.