ClinGen Dosage Sensitivity Curation Page

6q24 region (includes PLAGL1)

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
16971482 Diatloff-Zito et al. (2007) reported an ~365-kb heterozygous deletion in one patient with TNDM and severe congenital anomalies. No information was provided regarding inheritance status.

Evidence for Triplosenstive Phenotype

Evidence for triplosensitivity phenotype
PubMed ID Description
10615957 Cave et al. (2000) found paternal 6q24 duplications in 6 of 13 cases of TNDM.
8842729 Temple et al. (1996) reported that paternal transmission of a visible duplication of chromosome 6q24 leads to TNDM.
10923638 Temple et al. (2000) described 11 cases of TNDM in which qPCR identified paternally-derived submicroscopic duplications of 6q24

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.