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15q24 recurrent region (LCR A-LCR C) |
- 3
Haplo
Score - 1
Triplo
Score
Dosage Sensitivity Summary (Region)
Dosage ID:
ISCA-46296
Curation Status:
Complete
Issue Type:
Dosage Curation -
Region
Description:
The 15q24 region contains a cluster of low copy repeats (LCRs) that mediate recurrent copy number changes through non-allelic homologous recombination. This review refers to nested CNVs involving recurrent breakpoint regions LCR B and LCR C.
Note that genes used as landmarks are not necessarily causative of the phenotype(s) associated with the region.
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
Little Evidence for Triplosensitivity
(1)
Related Links:
Last Evaluated:
01/03/2020
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Evidence:
-
PUBMED:
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.
-
PUBMED:
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.
HI Evidence Comments:
Deletion of the 15q24 recurrent region (A-C)** has been reported in at least 5 patients in association with a clinical phenotype characterized by developmental delays (speech and motor), intellectual disability, brain anomalies, craniofacial abnormalities, hypotonia, ocular abnormalities, hearing loss, and other variable clinical features. In all cases where parental studies have been performed, deletions were found to be de novo.
**Note - Deletions involving the 15q24A-D region are covered in a separate region review.
Additional relevant literature is summarized below:
Reviews:
PMID 22359776: GeneReviews. Mefford, Shur, Rosenfeld.
PMID 22216833: Chromosome 15q24 microdeletion syndrome. Magoulas and El-Hattab (2012).
Case-control studies:
PMID 25217958: Coe et al. (2014)
In a large-scale case-control comparison study of the relative prevalence of copy number variants in children with ID/DD, MCA, and other developmental phenotypes compared to presumably unaffected adult controls, the 15q24 LCRA-C deletion was observed in 7/29,085 cases versus 0/19,584 controls (p=0.027; LR: Inf, CI: 1.23 to Inf), providing evidence for enrichment of this deletion in the clinical population.
Triplosensitivity (TS) Score Details
TS Score:
1
TS Evidence Strength:
Little Evidence for Triplosensitivity (Disclaimer)
TS Published Evidence:
-
PUBMED: 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.
-
PUBMED: 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.
TS Evidence Comments:
Duplication of the 15q24 recurrent region (A-C) has been reported in two patients (from two families) with variable clinical findings. In addition, one patient with a duplication partially overlapping this region (B-D) has also been reported (summarized below).
Due to the limited number of reported cases involving this region, phenotypic variability, evidence for reduced penetrance from parental studies in one case, and insufficient significance estimates from case-control studies (due to a limited number of observations), the current triplosensitivity score is 1.
Additional relevant literature is summarized below:
PMID 18755302
Kiholm Lund et al. (2008) reported a single patient with a 15q24 LCRB-D duplication. This patient presented with global developmental delay (speech and motor), abnormal MRI findings (agenesis of the corpus callosum, dilation of the lateral ventricles, and a small hemorrhage of the left parital region), hypertonia, craniofacial dysmorphisms, digital anomalies, hypospadias, eye anomalies, ear infections, and additional minor phenotypic features. The duplication was inherited from the father, who was reportedly unaffected.
Case-control studies:
PMID 25217958: Coe et al. (2014)
In a large-scale case-control comparison study of the relative prevalence of copy number variants in children with ID/DD, MCA, and other developmental phenotypes compared to presumably unaffected adult controls, the 15q24 LCRA-C duplication was observed in 3/29,085 cases versus 0/19,584 controls (p=0.2130; LR: Inf, CI: 0.356 to Inf).
