General information
The SALSA MLPA
Probemix P075 TCF4-FOXG1 is a
research use only (RUO) assay for the detection of deletions or duplications in the
TCF4 and
FOXG1 genes, which are associated with Pitt-Hopkins syndrome (PTHS).
PTHS is a rare disorder characterized by severe intellectual disability, pervasive developmental delay, ‘atypical’ autistic characteristics, and hyperventilation. PTHS is caused by heterozygous hypomorphic or null mutation or deletion of the transcription factor 4 (
TCF4;
E2-2;
ITF2) gene on human chromosome 18. The
TCF4 gene is also a risk factor with highly significant linkage to schizophrenia, presumably via overexpression of the
TCF4 gene product in the central nervous system.
Another disorder that has some phenotypical overlap with PTHS is the congenital variant of Rett syndrome. This syndrome occurs almost exclusively in females and is characterized by hypotonia and intellectual disability from the very first months of life. It has been reported that the main cause of the congenital variant of Rett syndrome is mutations in the
FOXG1 gene, which encodes a transcription factor of the forkhead family on chromosome 14.
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK100240/.
This SALSA MLPA probemix is not CE/FDA registered for use in diagnostic procedures. Purchase of this product includes a limited license for research purposes.
Probemix content
The SALSA MLPA Probemix P075-B2 TCF4-FOXG1 contains 50 MLPA probes with amplification products between 130 and 485 nucleotides (nt). This includes 35 probes for the
TCF4 gene covering all exons, with additional probes for exons 1, 4, 5, 6, 9, 11, and 20, and four intronic probes and four probes located upstream of
TCF4, most of them detecting exons of other transcript variants. Furthermore, five probes for the
FOXG1 are included
, two probes upstream of the gene and three probes targeting exon 1. In addition, ten reference probes are included that detect autosomal chromosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes are available online (
www.mrcholland.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.mrcholland.com.