ClinGen Dosage Sensitivity Curation Page

15q25.2q25.3 recurrent region (LCR C-D, distal)

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
23239641 Doelken, et al. (2013) described a male patient with three microdeletions, including a microdeletion of the 15q25.2q25.3 region (LCR C-D, distal). He had severely delayed psychomotor and language development, epileptiform signs by EEG, plagiocephaly, microcephaly, dysmorphic craniofacial features (which included strabismus, myopathic facies, hypoplastic nasal alae, bitemporal sparse hair), camptodactyly of the 5th fingers, left-sided retractile testis, and recurrent infections. The 15q25.2q25.3 deletion was inherited from a healthy father. Additionally, this patient had a 1q21.1 deletion (maternal inheritance) and a de novo hemizygous deletion of the Xq12 region (including OPHN1). Therefore, the authors acknowledge that the patient's clinical findings might be the result of the combination of the three microdeletions.

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.