FGF10 missense mutations in aplasia of lacrimal and salivary glands (ALSG)

Abstract

Aplasia of lacrimal and salivary glands (ALSG) is an autosomal dominant congenital anomaly characterized by aplasia, atresia or hypoplasia of the lacrimal and salivary systems. Affected individuals present with irritable eyes and dryness of the mouth with variable expressivity. Mutations in FGF10 were recently described in ALSG and in lacrimo-auriculo-dento-digital (LADD) syndrome which are overlapping clinical entities. We present here two families with ALSG associated with missense mutations (R80S and G138E, respectively) affecting highly conserved residues in FGF10. The clinical features of these patients further broaden the knowledge of FGF10-related phenotypes.

Functional evolutionary history of the mouse Fgf gene family

“…FGF23 also functions as a humoral phosphaturic factor responsible for tumor-induced osteomalacia (Shimada et al, 2001). Both aplasia of lacrimal and salivary glands and lacrimo-auriculo-dento-digital syndrome are caused by mutations in FGF10 (Entesarian et al, 2005(Entesarian et al, , 2007 2006). Michel aplasia is caused by mutations in FGF3 (Tekin et al, 2007).…”

The Fgf Families in Humans, Mice, and Zebrafish: Their Evolutional Processes and Roles in Development, Metabolism, and Disease

“…Both ALSG and LADD are caused by FGF10 mutations. [74][75][76][77] We originally identified Fgf20 as a neurotrophic factor preferentially expressed in dopaminergic neurons within the substantia nigra pars compacta of rat brain. 20) Parkinson disease (PD) is caused by a pathogenic process responsible for the loss of dopaminergic neurons within the substantia nigra pars compacta.…”

Interrogation of a lacrimo-auriculo-dento-digital syndrome protein reveals novel modes of fibroblast growth factor 10 (FGF10) function

“…predicted to generate a truncated non-functional protein (Table 1). However, the mechanism by which the third mutation -a Glycine (G) to Glutamic Acid (E) substitution at residue 138 -causes LADD [4] is unknown, and its apparent lack of involvement in receptor binding has raised the interesting possibility that FGF10 functions in multiple ways. Typically, FGF10 is secreted by mesenchymal cells to regulate epithelial cell growth and branching morphogenesis by activating the epithelially-expressed FGFR2-IIIb isoform [9][10][11].…”