Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm

Abstract

Fgfrl1 (also known as Fgfr5; OMIM 605830) homozygous null mice have thin, amuscular diaphragms and die at birth because of diaphragm hypoplasia. FGFRL1 is located at 4p16.3, and this

An integrated genomic, transcriptional and protein investigation of FGFRL1 as a putative 4p16.3 deletion target in bladder cancer

“…Previously described polymorphisms of FGFRL1 were identified in some samples, including the rs4647930 C/A polymorphism in exon 7, which results in a proline to glutamine change in the membrane-proximal region of the protein (P362Q). Interestingly, in the tumor tissue, the frequency of the rare A allele was higher than expected according to the previously reported frequencies (0.500 vs 0.275) (LopezJimenez et al, 2010). Analysis of matched blood samples suggested that in heterozygous patients with 4p16.3 LOH, the common C allele was preferentially lost in the tumor tissue (6/8, 75%) (Table 1) but numbers are too small to draw any definitive conclusion.…”

“…FGFRL1 genomic sequence was obtained from publically available databases (http://www.ensembl.org, http://www.ncbi.nlm.nih.gov), and exons were annotated and numbered consistently with Lopez‐Jiminez et al (LopezJimenez et al, ). Of the six coding exons, five (exons 2, 3, 4, 6, and 7) were screened for mutations using high resolution melting (HRM) followed by bidirectional dye‐termination sequencing of samples with altered melting profile.…”

Congenital diaphragmatic hernia and a complex heart defect in association with Wolf–Hirschhorn syndrome

“…Moreover, deletion of the first 1.4 Mb region of chromosome 4p has been observed in nonaffected individuals as well [South et al, 2008a] questioning its pathogenic role. Finally, deletions of the FGFRL1 gene were not observed in array-CGH analysis of CDH patient cohorts [Scott et al, 2007] nor in mutation analysis of the FGFRL1 gene [LopezJimenez et al, 2009]. However the CDH patients screened in these studies were not specifically selected for both CDH and WHS associated anomalies such as craniosynostosis.…”

Biology of FGFRL1, the fifth fibroblast growth factor receptor

“…Since Fgfrl1-deficient mice have a hypoplastic diaphragm, the FGFRL1 gene was searched for mutations in 54 patients with congenital diaphragmatic hernia. Six established polymorphisms were found, but no novel gene mutations [58]. The database of single nucleotide polymorphisms, dnSNP (http://www.ncbi.nlm.nih.…”

“…Only three of these SNPs occur with significant frequency in the Caucasian population, namely P362Q, R424L, and P464L, and all these SNPs are located within the last exon of the FGFRL1 gene. One congenital diaphragmatic hernia patient was found to be hemizygous for the minor allele of two nonsynonymous SNPs (P362Q, P464L) [58]. It is therefore conceivable that these polymorphisms predispose the patient to diaphragmatic hernia.…”