ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
15654336 Entesarian et al. (2005) report 16 individuals from two extended families of Swedish origin with full penetrant aplasia of lacrimal and salivary glands (ALSG). The 12 affected members of family 1 (4 generations) had a 53 kb deletion including exons 2 and 3, without the involvement of any flanking genes. In family 2 (3 generations) , a nonsense variant in exon 3 (R193X; c.577C>T) was identified in the four affected members.
16630169 Milunsky et al. (2006) identified a nonsense mutation (K137X) in exon 2 of FGF10 (Family 2) in a 19-year-old mother with ALSG and her 2-year-old daughter with Lacrimoauriculodentodigital (LADD) syndrome. This variant was not found in 200 controls. The author concluded that ALSG and LADD syndrome may represent variable presentations of the same clinical spectrum caused by FGF10 mutations.
19102732 Scheckenbach et al. (2008) identified the 1st splicing variant (c.430-1 G>A) in FGF10 gene, which led to an alternative acceptor site for exon 3 and premature stop codon, in 2 affected brothers with ALSG, but not in 193 controls. Patients? father, grandma and grandaunt were all affected, but not available for testing. Deceased relatives showed no additional features of LADD.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.