General Information: The SALSA MLPA Probemix P133 Kallmann-2 is a research use only (RUO) assay for the detection of deletions or duplications in several genes associated with Kallmann syndrome.
Kallmann syndrome is a disease of idiopathic hypogonadotropic hypogonadism with anosmia or hyposmia. Defects in several genes can result in a Kallmann syndrome phenotype. This P133-C2 SALSA MLPA probemix contains probes for the FGFR1, GNRHR, KISS1R (GPR54), GNRH1, NELF, PROK2 and PROKR2 genes, which are involved, or suspected to be involved, in Kallmann syndrome.
Loss-of-function mutations in FGFR1 underlie Kallmann syndrome 2 (KAL2), whereas a gain-of-function mutation in FGFR1 has been shown to cause a form of craniosynostosis. The FGFR1 gene (18 exons) spans ~58 kb of genomic DNA and is located on chromosome 8p12, 38 Mb from the p-telomere. This P133-C2 Kallmann-2 probemix contains 11 probes for 10 of the 18 exons of the FGFR1 gene.
Defects in the KISS1R gene are a possible cause of hypogonadotropic hypogonadism. The KISS1R gene (5 exons) spans ~4 kb of genomic DNA and is located on chromosome 19p13.3, 0.9 Mb from the p-telomere. This probemix contains probes for 3 of the 5 exons of the KISS1R gene.
A candidate gene for the autosomal form of Kallmann syndrome is the NELF (NSMF) gene. The NELF gene (16 exons) spans ~12 kb and is located on chromosome 9q34.3, 137 Mb from the p-telomere. This P133-C2 Kallmann-2 probemix contains probes for 3 of the 16 exons of the NELF gene.
An autosomal recessive form of Kallmann syndrome can be caused by defects in the GNRH1 gene. The GNRH1 gene comprises 3 exons and spans ~5 kb on chromosome 8p21.2, 25 Mb from the p-telomere. Probes for each exon of the GNRH1 gene are included in this probemix.
Defects in the GNRHR gene are a cause of hypogonadotropic hypogonadism without anosmia. The GNRHR gene (3 exons) spans ~19 kb and is located on chromosome 4q13.2, 68 Mb from the p-telomere. Probes for each exon of the GNRHR gene are included in this probemix.
The PROK2 and PROKR2 genes have been implicated in autosomal recessive Kallmann syndrome (Abreu et al. 2008). The PROK2 gene (4 exons) spans 14 kb on chromosome 3p13, 72 Mb from the p-telomere. The PROKR2 gene (3 exons), spans 12 kb and is located on chromosome 20p12.3, 5 Mb from the p-telomere. Probes for each of the four PROK2 exons and for two PROKR2 exons have been included in this P133-C2 probemix.
Probemix content: The SALSA MLPA Probemix P133-C2 Kallmann-2 contains 41 MLPA probes with amplification products between 130 and 454 nt. This includes 31 probes for the different genes associated with Kallmann syndrome. In addition, 10 reference probes are included and detect 10 different autosomal chromosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes is available online (www.mlpa.com).
This Probemix contains nine quality control fragments generating amplification products between 64 and 121 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.