ClinGen Dosage Sensitivity Curation Page

15q11q13 recurrent (PWS/AS) region (BP1-BP3, Class 1)

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
7611294 Christian et al. (1997) characterized the two proximal breakpoints in 80 individuals with either Angelman or Prader-Willi syndrome. 44% were shown to have the class I deletion, while 56% were found to have the class II deletion (45/80). No phenotypic difference between class I and class II deletions were noted.
22045295 Kim et al. (2012) describe 88 patients with Prader-Willi syndrome, 32 had the type I deletion (36%), 49 had the type II deletion (56%) and the remaining 7 had atypical deletions.

Evidence for Triplosenstive Phenotype

Evidence for triplosensitivity phenotype
PubMed ID Description
9106540 Cook et al. (1997) describe a family in which two children with autism spectrum disorders inherited a 15q11-q13 duplication from their reportedly normal mother. The duplication was found to have arisen de novo on the mother's paternally inherited allele. A third child who was reportedly unaffected did not inherit the duplication.
18374305 Christian et al. (2008) identified three maternally inherited 15q11-q13 duplications amongst a cohort of 397 unrelated individuals with autism spectrum disorders.
16840569 Jacquemont et al. (2006) identified one de novo 15q11-q13 duplication, derived from the maternal allele, in a female with autism and mild intellectual disability

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.