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Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence that the FGFR1c isoform is required in olfactory bulb and palate morphogenesis
Author(s) -
Dodé Catherine,
Fouveaut Corinne,
Mortier Geert,
Janssens Sandra,
Bertherat Jérôme,
Mahoudeau Jacques,
Kottler MarieLaure,
Chabrolle Christine,
Gancel Antoine,
François Inge,
Devriendt Koen,
Wolczynski Slawomir,
Pugeat Michel,
PineiroGarcia Alfons,
Murat Arnaud,
Bouchard Philippe,
Young Jacques,
Delpech Marc,
Hardelin JeanPierre
Publication year - 2007
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9470
Subject(s) - biology , kallmann syndrome , olfactory bulb , morphogenesis , gene isoform , genetics , anatomy , olfactory system , neuroscience , gene , medicine , central nervous system , disease , covid-19 , infectious disease (medical specialty)
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. © 2006 Wiley‐Liss, Inc.