ClinGen Dosage Sensitivity Curation Page

15q24 recurrent region (A-C)

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
22180641 Mefford et al. (2012) reported four patients (Patients 2-5) with 15q24 LCRA-C deletions. These patients presented with developmental delays (including motor and speech), intellectual disability, craniofacial dysmorphisms, ocular anomalies, ear anomalies (including infections and hearing loss), hypotonia, abnormal behaviors, variable skeletal and skin anomalies, and additional variable clinical findings. Inheritance testing was completed in three of the four patients, and in each case the deletion was found to be de novo.
19921647 Andrieux et al. (2009) reported a single patient (Patient 3) with a 15q24 LCRA-C deletion. This patient presented with developmental delay (speech and motor), hypoplastic olfactory bulbs by MRI, ocular anomalies, hearing loss, asymmetric dysplastic ears, thin upper lip, widely spaced teeth, tetralogy of Fallot, and dry skin. Parental testing showed that this deletion was de novo.

Evidence for Triplosenstive Phenotype

Evidence for triplosensitivity phenotype
PubMed ID Description
19557438 El-Hattab et al. (2009) reported a single patient (Case 5) with a 15q24 LCRA-C duplication. This patient presented with short stature, mild intellectual disability, hypertonia, craniofacial abnormalities, decreased joint range of motion, digital anomalies, and behavioral abnormalities. The reported craniofacial features included a long face, down-slanting palpebral fissures, puffy eyelids, ptosis, smooth philtrum, and retrognathia. Maternal testing for this duplication was negative, but the father was not available for inheritance testing.
20860070 El-Hattab et al. (2010) reported a single patient with a 15q24 LCRA-C duplication, as well as a maternally inherited 2.4 Mb 16q22 duplication. The patient died in infancy, and had IUGR, FTT, craniofacial abnormalities (flat philtrum and puffy eyelids), cardiac anomalies (ASD, VSD, PDA, PS, and dextrocardia), heterotaxy, gastrointestinal obstruction, hydronephrosis, and additional clinical findings. The 15q24 LCRA-C duplication was paternally inherited; the patient?s father was reported to have congenital heart disease.

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.