ClinGen Dosage Sensitivity Curation Page

15q24 recurrent region (A-D) (includes SIN3A)

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 6-9) with 15q24 LCRA-D deletions. Clinical findings in common included growth delay/short stature, developmental delays (including motor and speech), intellectual disability, craniofacial dysmorphisms, ocular anomalies, hearing loss and/or ear infections/anomalies, hypotonia, variable skeletal anomalies, and additional variable clinical findings. Inheritance was de novo in three cases and unknown in one case (patient 6).
19557438 El-Hattab et al. (2009) reported two patients (Cases 3 and 4) with 15q24 LCRA-D deletions. Clinical findings in common included developmental delay/intellectual disability, mild and variable craniofacial anomalies, hypotonia, genital anomalies, skeletal anomalies (including joint laxity and digital anomalies), recurrent ear infections, skin findings, and other variable findings. Inheritance was de novo for both cases.
19233321 Van Esch et al. (2009) describe a single patient with a 15q24 LCRA-D deletion. This patient presented with developmental delay (speech and motor), intellectual disability, craniofacial abnormalities, hypotonia, scoliosis, talipes equinovarus (club foot), diaphragmatic hernia, digital anomalies, genital abnormalities, and behavioral problems. Inheritance was de novo.

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.