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7q11.23 recurrent distal region (includes HIP1, YWHAG) |
- 2
Haplo
Score - 1
Triplo
Score
Dosage Sensitivity Summary (Region)
Dosage ID:
ISCA-46291
Curation Status:
Complete
Issue Type:
Dosage Curation -
Region
Description:
The 7q11.23 region contains a cluster of low copy repeats (LCR) that mediate recurrent copy number changes through non-allelic homologous recombination. This review refers to CNVs involving recurrent breakpoint regions LCR-C and LCR-D.
Note that genes used as landmarks are not necessarily causative of the phenotype(s) associated with the region.
Haploinsufficiency:
Emerging Evidence for Haploinsufficiency
(2)
Triplosensitivity:
Little Evidence for Triplosensitivity
(1)
Last Evaluated:
04/20/2023
Haploinsufficiency (HI) Score Details
HI Score:
2
HI Evidence Strength:
Emerging Evidence for Haploinsufficiency
(Disclaimer)
HI Evidence:
-
PUBMED:
21109226
Ramocki et al. (2010) report 6 patients with recurrent 7q11.23 distal deletions from a large cohort of individuals (~29,510) referred for chromosomal microarray. Common clinical findings in these individuals included seizures (all patients), global developmental delay and intellectual disability, hyperactivity, and autism spectrum disorder. The recurrent deletion was not identified in over 20,000 individuals in a control cohort. All patients with informative parental testing were found to have an inherited deletion, with carrier parents having a history of epilepsy and/or mild intellectual disability/learning difficulties.
-
PUBMED:
35481155
Birca et al. (2022) report 3 patients with the recurrent 7q11.23 distal deletion from a two-generation family. The deletion was observed in the proband, his two maternal half-brothers, and their mother. The proband and one half-sibling presented with epilepsy with myoclonic-atonic seizures. All 3 siblings had developmental impairment/intellectual disability and neurobehavioral abnormalities. The mother was reported to have developmental impairment and learning difficulties. Additional maternal family members were reported to have similar phenotypes but were not tested for the presence or absence of the deletion.
-
PUBMED:
16971481
Edelmann et al. (2007) report a single patient from an autism cohort with a de novo recurrent 7q11.23 distal deletion. The deletion was. The clinical features described in this patient included developmental delay, autism, intellectual disability, and dysmorphic craniofacial findings that included asymmetric abnormally shaped ears, midface hypoplasia, bulbous nasal tip, wide spaced teeth, wide mouth, and prominent lips.
HI Evidence Comments:
Evidence in support of the pathogenicity of the recurrent 7q11.23 distal region deletion is emerging at this time. Deletions of this region have been reported in 10 patients with neurodevelopmental phenotypes, including seizures. Most of the reported deletions have been inherited from similarly affected parents, though it has also been found to represent a de novo event. Case-control studies, where performed, have a limited overall number of cases, and enrichment of this deletion has not been established in the clinical population. Therefore, the haploinsufficiency score is 2. Additional clinical reports, supportive case-control data, and/or establishment of a haploinsufficient gene within the deleted region will be required to assign this region a 3 score.
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 recurrent 7q11.23 distal region were observed in 5/29,085 cases versus 0/19,584 controls (p= 0.0762; LR: INF, 95% CI: 0.0775 to INF), with limited numbers and no evidence of enrichment of this CNV in the clinical population. See also Rosenfeld et al. (2013) (PMID 23258348) and Cooper et al. (2011) (PMID 21841781), which use overlapping (older) datasets.
Additional case reports:
PMID: 26437767
Nicita et al. (2016) reported a single individual with a de novo distal 7q11.23 deletion from a cohort of patients with a clinical diagnosis of Williams-Beuren Syndrome or distal 7q11.23 deletion syndrome with least two documented afebrile seizures. In addition to seizures, they had hyperactivity and language delay.
PMID: 30866059
Coppola et al. (2019) reported a single individual with a distal 7q11.23 deletion from a cohort of 1,255 patients with epilepsy and additional comorbid features. This deletion was maternally inherited. No additional phenotypic details were provided for this individual or their mother.
Triplosensitivity (TS) Score Details
TS Score:
1
TS Evidence Strength:
Little Evidence for Triplosensitivity (Disclaimer)
TS Published Evidence:
-
PUBMED: 21109226
Ramocki et al. (2010) reported a patient from a cohort of individuals referred for chromosomal microarray with a recurrent 7q11.23 distal duplication. The clinical features described in this patient included bipolar disorder, ADHD, and aggression. The patient’s sister also carried the duplication and had speech delay, ADHD and aggression. Maternal inheritance was excluded, and a paternal sample was not available for testing.
-
PUBMED: 27867344
Faundes et al. (2016) reported a patient a de novo recurrent 7q11.23 distal duplication. The clinical features described in this individual include dysmorphic features (broad face, straight eyebrows, deep-set eyes, protruding nasal tip, and high-arched palate), obesity, hyperphagia, intellectual disability, speech delay, motor developmental delay, and behavioral differences including aggressiveness and ADHD.
TS Evidence Comments:
Evidence in support of the pathogenicity of the recurrent 7q11.23 distal region duplication is limited at this time. Duplications of this region are rare in the literature, with 3 cases from two families reported across 2 studies. Amongst affected carriers, clinical findings are mostly nonspecific, including ADHD, aggressive behavior, speech delay and other variable findings. Due to the limited number of reported cases with variable inheritance and lack of parental phenotype information, inheritance and penetrance are not well-understood. Case-control comparison studies have not shown enrichment of this duplication in clinical populations. Therefore, the triplosensitivity score is 1.
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 7q11.23 recurrent distal region were observed in 1/29,085 cases versus 0/19,584 controls (p=0.598; LR: INF, 95% CI: 0.0364-INF), with no evidence of enrichment of this CNV in the clinical population.
Genomic View
Select assembly:
(NC_000007.13)
()
