Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands

  title={Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands},
  author={Miriam Entesarian and Hans Matsson and Joakim Klar and Birgitta Bergendal and L. Olson and Rieko Arakaki and Yoshio Hayashi and Hideyo Ohuchi and Babak Falahat and Anne Isine Bolstad and Roland Jonsson and Marie Wahren-Herlenius and Niklas Dahl},
  journal={Nature Genetics},
Autosomal dominant aplasia of lacrimal and salivary glands (ALSG; OMIM 180920 and OMIM 103420) is a rare condition characterized by irritable eyes and dryness of the mouth. We mapped ALSG to 5p13.2–5q13.1, which coincides with the gene fibroblast growth factor 10 (FGF10). In two extended pedigrees, we identified heterozygous mutations in FGF10 in all individuals with ALSG. Fgf10+/− mice have a phenotype similar to ALSG, providing a model for this disorder. We suggest that haploinsufficiency for… 
FGF10 missense mutations in aplasia of lacrimal and salivary glands (ALSG)
Two families with ALSG associated with missense mutations (R80S and G138E, respectively) affecting highly conserved residues in FGF10 are presented and the clinical features of these patients further broaden the knowledge of FGF 10-related phenotypes.
Novel FGF10 mutation in autosomal dominant aplasia of lacrimal and salivary glands
It is confirmed that ALSG is caused by the haploinsufficiency of functional FGF10, and will positively motivate oral health care to avoid further destruction of the tooth due to the lack of salivary production.
Mutations in different components of FGF signaling in LADD syndrome
Heterozygous mutations in the tyrosine kinase domains of the genes encoding fibroblast growth factor receptors 2 and 3 in LADD families, and in one further LADD family, are detected, increasing the spectrum of anomalies associated with abnormal FGF signaling.
Case report: aplasia of the lacrimal and major salivary glands (ALSG).
Interrogation of a lacrimo-auriculo-dento-digital syndrome protein reveals novel modes of fibroblast growth factor 10 (FGF10) function.
FGF10 harbours two putative nuclear localization sequences (NLSs), termed NLS1 and NLS2, which individually or co-operatively promote nuclear translocation of FGF10, which suggests that in addition to its paracrine roles, FGF 10 may normally play intracrine role/s within F GF10-producing cells.
Aplasia of the lacrimal and major salivary glands (ALSG). First case report in spanish population and review of the literature
In this case, a 40 years male patient diagnosed with complete agenesis of all salivary glands is the first of ALSG syndrome in the Spanish literature.
Deletion of the last two exons of FGF10 in a family with LADD syndrome and pulmonary acinar hypoplasia
A multi-generational family with seven members manifesting varying features of LADD syndrome, with one individual dying in early infancy of PAH, identifies a 12,158 bp deletion on chromosome 5p12 that removes two of the three exons of FGF10 and concludes the deletion is pathogenic and expands the mutational spectrum of F GF10 variants in Ladd syndrome.
Lacrimo-Auriculo-Dento-Digital Syndrome Is Caused by Reduced Activity of the Fibroblast Growth Factor 10 (FGF10)-FGF Receptor 2 Signaling Pathway
These experiments show that the biological activities of three different FGF10 LADD mutants are severely impaired by different mechanisms and that relatively small changes in receptor signaling may influence the outcome of developmental processes in cells or organs that do not possess redundant signaling pathway.
Salivary Gland Dysplasia in Fgf10 Heterozygous Mice: A New Mouse Model of Xerostomia
Analysis of saliva secretion showed that hypoplasia of the glands led to a significant reduction in saliva production in Fgf10 +/- adults, giving rise to a reduced saliva pellicle in the oral cavity of these mice.
Salivary Gland Diseases
The genetic mutations that underlie autosomal dominant, autosomal recessive, and X-linked salivary gland abnormalities are discussed, as well as the role of genetic factors on the predisposition and phenotypic variation of other autoimmune and granulomatous disorders.


Salivary gland disorders and heredity.
  • H. Wiedemann
  • Medicine
    American journal of medical genetics
  • 1997
From personal observations, I review the genetic disorders of salivary gland development and function, including the lacrimo-auriculodentodigital (LADD) syndrome, autosomal dominant
Genetic aspects of Sjögren's syndrome
The present review synthesizes the current state of genetics in Sjögren's syndrome and recommends further advances in molecular and genetic methodologies to further the understanding of this complex disease.
Agenesis or hypoplasia of major salivary and lacrimal glands.
We described a young man with almost total absence of the parotid glands, hypoplasia of both lacrimal glands, marked hypofunction of both submandibular glands, and left nasolacrimal duct atresia.
An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis.
Findings point to a key role for fibroblast growth factor receptor 2(IIIb) in mesenchymal-epithelial signalling during early organogenesis.
Congenital absence of lacrimal puncta and salivary glands: report of a Brazilian family and review.
The first Brazilian observation of this syndrome is presented and a review of the literature is presented, revealing a rare autosomal-dominant disorder with variable expressivity.
FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development.
Results suggest that FGF10 acts as a major ligand for FGFR2b in mouse multi-organ development, which would indicate a role for FGF12 in wide-range organogenesis.
FGF10 is an inducer and Pax6 a competence factor for lacrimal gland development.
It is shown that fibroblast growth factor (FGF) 10 is sufficient to stimulate ectopic Lacrimal bud formation in ocular explants and that FGF10 combines with other factors to provide the instructive signals required for lacrimal gland development.
Fibroblast Growth Factor-10 Is a Mitogen for Urothelial Cells*
The normal urothelial phenotype, that of quiescence, is proposed to be typified by negligible levels of FGF-10, during proliferative phases, as well as a signaling cascade that begins with the heparin-dependent phosphorylation of tyrosine residues of surface transmembrane receptors.
Fgf10 is essential for limb and lung formation
It is shown that Fgf10 serves as an essential regulator of lung and limb formation in mice generated with F gf10-deficient mice.
Syndromes with salivary dysfunction predispose to tooth wear: Case reports of congenital dysfunction of major salivary glands, Prader-Willi, congenital rubella, and Sjögren's syndromes.
Four cases-of congenital dysfunction of the major salivary glands as well as of Prader-Willi, congenital rubella, and Sjögren's syndromes-were identified in a series of 500 patients referred for excessive tooth wear, underline the importance of normal salivation in the protection of teeth against tooth wear by erosion, attrition, and abrasion.