General information
The SALSA MLPA
Probemix P154 GPC3-GPC4 is a
research use only (RUO) assay for the detection of deletions or duplications in the
GPC3 and
GPC4 genes, which are associated with Simpson-Golabi-Behmel syndrome type 1.
Simpson-Golabi-Behmel syndrome (SGBS) type 1 is an X-linked overgrowth syndrome associated with multiple congenital anomalies caused by a mutant X-linked recessive trait. Alternative names are: Bulldog syndrome; dysplasia gigantism syndrome X-linked (DGSX), Golabi-Rosen syndrome, Simpson dysmorphia syndrome (SDYS). SGBS shows a broad spectrum of clinical manifestations, varying from mild forms in carrier females to infantile lethal forms in affected males. The most consistent findings are pre- and postnatal macrosomia, characteristic coarse "bulldog-like" face and a complex assortment of congenital defects affecting the internal organs and skeleton. On some occasions, intellectual disability of variable degree is observed. SGBS is also associated with an increased risk of developing embryonal neoplasia, mostly Wilms and liver tumours. SGBS type 2 is a rarer, more lethal form with different genes involved.
SGBS type 1 is caused by mutations in the glypican 3 (
GPC3) and/or glypican 4 (
GPC4) genes, both located on chromosome Xq26. Around 43% of
GPC3 pathogenic variants is a deletion or duplication. Alternative names for the
GPC3 gene are
SGBS,
SGBS1,
SGB and
DGSX. The glypicans (GRIPS) are a family of cell surface heparan sulphate proteoglycans that are bound to the cell surface and they may play a role in the control of cell division and growth regulation. Glypicans are anchored to the peripheral membrane through glycosylphosphatidylinositol (GPI) linkage. Deletions in the
GPC3 gene have been found in a number of SGBS
families supplying evidence that such mutations are responsible
for SGBS. Duplication of the
GPC4 gene has been described in one SGBS family (Waterson et al. 2010). The tight clustering of
GPC3 and
GPC4 may be relevant for explaining the variability of the SGBS phenotype.
The
GPC3 gene (8 exons) spans ~450 kb of genomic DNA and is located on chromosome Xq26.2, 132 Mb from the p-telomere. The
GPC4 gene (9 exons) spans ~115 kb of genomic DNA and is located on chromosome Xq26.2, centromeric to
GPC3.
More information is available at
https://www.ncbi.nlm.nih.gov/books/NBK1219/.
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 P154-C2 GPC3-GPC4 contains 37 MLPA probes with amplification products between 136 and 454 nucleotides (nt). This includes 26 probes for the
GPC3 and
GPC4 genes: two probes for each exon of the
GPC3 gene (three probes for
GPC3 exon 1 and one for exon 5) and one probe for each exon of the
GPC4 gene (two probes for
GPC4 exon 1). In addition, 11 reference probes are included that detect locations on the X-chromosome. 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.