 |
22q11.2 recurrent region (distal type III, F-G) (includes SMARCB1) |
- 3
Haplo
Score - 0
Triplo
Score
Dosage Sensitivity Summary (Region)
Dosage ID:
ISCA-46294
Curation Status:
Complete
Issue Type:
Dosage Curation -
Region
Description:
Chromosome 22 contains a cluster of low copy repeats that mediate recurrent copy number changes through non-allelic homologous recombination. This review refers to the nested 22q11.2 recurrent region (distal type III) between breakpoints LCR22F and LCR22G.
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:
No Evidence for Triplosensitivity
(0)
Related Links:
Last Evaluated:
09/30/2022
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Evidence:
-
PUBMED:
21208904
Bourdeaut et al (2011) report a single patient with a 22q11.2 deletion involving LCR22F to LCR22G. This patient was identified in a large cohort of patient with rhabdoid tumors. The patient presented with atypical/teratoid rhabdoid tumors and was dead of disease at age 3. No additional clinical information was provided. Parental testing was performed on the majority of patients in their cohort; however, it was not specifically stated whether the patient with the LCR22F to LCR22G was one of them.
HI Evidence Comments:
The haploinsufficiency score for this region is based on evidence for a gene (SMARCB1) encompassed by this region (see linked gene review). SMARCB1 haploinsufficiency is associated with rhabdoid tumor predisposition syndrome. Therefore, the haploinsufficiency score is 3.
In the context of neurodevelopmental phenotypes, evidence supporting the significance of the F-G region is absent. Focal deletions of the F-G region are rare in the literature and focus on predisposition to rhabdoid tumors. Due to the limited number of reported cases and lack of proband and parental phenotype information, the possible neurodevelopmental impact, if any, of focal deletions of this region is unknown.
Of note, patients with larger deletions involving 22q11.2 LCR22 E/F-H have been reported. These are being reviewed separately.
Additional relevant literature is summarized below:
Case-Control Studies:
PMID: 25217958
Coe et al. (2014) performed a large-scale case-control comparison study of the relative prevalence of CNVs in children with developmental delay/intellectual disability, multiple congenital anomalies, and other developmental phenotypes compared to controls. Deletions of the 22q distal type III F-G region were observed in 7/29,085 cases versus 2/19,584 controls (p=0.2273; LR: 2.36, 95% CI: 0.523 to 13.7), with limited numbers and no evidence of enrichment of this CNV in the clinical population.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
At this time there are no reported patients with isolated duplications involving the 22q11.2 distal type III F-G duplication. Therefore, the triplosensitivity score for this region is a 0.
Of note, patients with larger duplications involving 22q11.2 LCR22 E/F-H have been reported. These are being reviewed separately.
Additional literature is summarized below:
Case-Control Studies
PMID: 25217958
Coe et al. (2014) performed a large-scale case-control comparison study of the relative prevalence of CNVs in children with developmental delay/intellectual disability, multiple congenital anomalies, and other developmental phenotypes compared to controls. Duplications of the 22q11.2 distal type III F-G region were observed in 12/29,085 cases versus 3/19,584 controls (p=0.087; LR: 2.69, 95% CI: 0.829 – 10.2), no evidence of enrichment of this CNV in the clinical population.
