Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence that the FGFR1c isoform is required in olfactory bulb and palate morphogenesis
✍ Scribed by Catherine Dodé; Corinne Fouveaut; Geert Mortier; Sandra Janssens; Jérôme Bertherat; Jacques Mahoudeau; Marie-Laure Kottler; Christine Chabrolle; Antoine Gancel; Inge François; Koen Devriendt; Slawomir Wolczynski; Michel Pugeat; Alfons Pineiro-Garcia; Arnaud Murat; Philippe Bouchard; Jacques Young; Marc Delpech; Jean-Pierre Hardelin
- Book ID
- 102265967
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 84 KB
- Volume
- 28
- Category
- Article
- ISSN
- 1059-7794
No coin nor oath required. For personal study only.
✦ Synopsis
In a new cohort of 141 unrelated patients affected by Kallmann syndrome we identified FGFR1 sequence variants in 17 patients, all in the heterozygous state. The fifteen novel variants consist of 10 missense (p.N77K, p.C101F, p.R250W, p.G270D, p.P283R, p.S332C, p.H621R, p.S685F, p.I693F, p.R822C), two nonsense (p.E324X, p.R661X), a frameshift (p.S439fs), and two splice site (c.1081G>C and c.1977+1G>A) changes. However, the p.N77K and p.R822C changes were also found in two and one out of 150 healthy control individuals, respectively, and therefore, their pathogenic effect is questionable. Notably, three alterations (p.E324X, p.S332C, c.1081G>C) are located in the alternative exon 8B that codes for the FGFR1c isoform, thus indicating that this isoform plays a crucial role in the development of the olfactory system in man. Moreover, the presence of cleft palate in a patient carrying the p.E324X change shows that FGFR1c is important for palate morphogenesis too.