ClinGen Dosage Sensitivity Curation Page

Gene Information

• id: ISCA-37449
• Date last evaluated: 2012-05-10
• Entrez Gene:

Location Information

• 14q32
• GRCh37/hg19 chr14: 100,394,594-101,504,529

Evidence for Loss Phenotypes

• Loss of function score: 2
• Strength of Evidence: Some evidence for dosage pathogenicity
• Haploinsufficiency phenotype: KAGAMI-OGATA SYNDROME

Evidence for loss of function phenotype

PubMed ID	Description
20179077	Bena et al. (2010): A report of a patient with a de novo deletion of this region, of paternal origin, who had a UPD(14)mat phenotype. They determined that this deletion was mediated by flanking (TGG)n tandem repeats. The deletion encompasses multiple genes, both imprinted and non-imprinted. The authors also show that the patient previously reported by Buiting et al (2008), see below, had the identical deletion.
18454453	Buiting et al (2008): A report of a patient with a deletion mediated by the flanking (TGG)n tandem repeats as described by Bena (2010) who had a UPD(14)mat phenotype. The deletion was paternally derived based on methylation-sensitive PCR, although the father was not available for testing.

• Loss of function phenotype comments: In addition to the two patients described above, there is one case in the ISCA database with a de novo deletion with the same breakpoints who had failure to thrive. The phenotype associated with this deletion would depend on the parental origin. Additional larger deletions that overlap this region have also been reported in individuals with UPD(14)mat and UPD(14)pat phenotypes (PMID: 18176563).

Evidence for Triplosenstive Phenotype

• Triplosensitivity score: 0
• Strength of Evidence: No evidence for dosage pathogenicity

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.