ClinGen Dosage Sensitivity Curation Page

2p24.3 MYCN-DDX1 duplication region

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for Triplosenstive Phenotype

Evidence for triplosensitivity phenotype
PubMed ID Description
27794475 Micale et al. (2016) describe a 13-month old boy with a 560 kb duplication at 2p24.3, involving the NBAS, DDX1, MYCNOS, and MYCN genes. His clinical features included hydrocephaly, ventricular septal defect, partial agenesis of the corpus callosum, and bilateral Wilms tumor. His mother was found to carry the same duplication with no clinical presentation suggesting incomplete penetrance.
24161495 Fievet et al. (2013) describe a 3-year-old girl and her father with a 569 kb duplication at 2p24.3, involving the NBAS, DDX1, MYCNOS, and MYCN genes. Both individuals presented with nephroblastoma, with the girl presenting prenatally with bilateral nephroblastomatosis. Both individuals also carried a chromosome 8 pericentric inversion; however, the authors were unable to establish a link between this finding and the renal tumors.
23401364 Van Mater et al. (2013) describe an 11-month old boy with a 1 Mb duplication at 2p24.3, involving the MYCN, MYCNOS,and DDX1 genes (partially including the FAM49A gene). His clinical features include high forehead, hypertelorism, postaxial polydactyly, and developmental delay. He developed Stage 4 neuroblastoma by 11 months of age. This duplication was de novo.

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.