Brain malformations in a patient with deletion 2p16.1: A refinement of the phenotype to BCL11A

Balci, Tugce B.; Sawyer, Sarah L.; Dávila, Jorge; Humphreys, Peter; Dyment, David A.

doi:10.1016/j.ejmg.2015.04.006

Cited by 25 publications

(40 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CNVs with the smallest number of deleted genes (1-4) were detected in 10 cases (Figure 2 and Supplemental Table 4). BCL11A was the only coding gene deleted in 2 cases (3,8). BCL11A was deleted along with PAPOLG in 1 patient (subject 2 in Basak et al, ref.…”

Section: Resultsmentioning

confidence: 98%

“…Since the initial report, detailed clinical phenotypes for 25 subjects have been reported, demonstrating common phenotypic abnormalities including delayed neurocognitive development, microcephaly, consistent and recognizable facial dysmorphism (telecanthus, broad and high nasal root, ptosis, long and smooth philtrum), feeding problems, a variety of head shape and structural brain abnormalities, hypotonia, and digital anomalies (reviewed previously in refs. [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8], and the existence of nonoverlapping copy number variants (CNVs) within the 2p15p16.1 deletion region complicate efforts to delineate a common critical region for the syndrome. In addition, some studies suggested that The 2p15p16.1 microdeletion syndrome has a core phenotype consisting of intellectual disability, microcephaly, hypotonia, delayed growth, common craniofacial features, and digital anomalies.…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, several deletions involving individual genes or smaller numbers of genes were reported (2)(3)(4)(5)(8)(9)(10) XPO1 (also known as CRM1) is a nuclear export receptor that exports approximately 200 different cargo molecules (e.g., proteins, rRNA, small nuclear RNA [snRNA], miR, and specific mRNAs) from the nucleus to the cytoplasm. This includes molecules required for correct neuronal positioning during development (20) or synaptogenesis (21).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis

Bagheri¹,

Badduke²,

Qiao³

et al. 2016

JCI Insight

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis

Bagheri¹,

Badduke²,

Qiao³

et al. 2016

JCI Insight

View full text Add to dashboard Cite

“…In addition, BCL11A is included in most CNVs reported as the 2p15‐p16.1 microdeletion syndrome (OMIM #612513), characterized by developmental delay, intellectual disability, hypotonia, poor verbal skills, craniofacial and skeletal features, digital anomalies, and fetal hemoglobin persistence (Basak et al, 2015; Funnell et al, 2015). When described, patients with 2p15p16 microdeletion encompassing BCL11A show delayed receptive and expressive language skills (Hancarova et al, 2013; Piccione et al, 2012; Rajcan‐Separovic et al, 2007), language delay (Balci, Sawyer, Davila, Humphreys, & Dyment, 2015; Felix, Petrin, Sanseverino, & Murray, 2010), language restricted to a few single words and signing (Florisson et al, 2013), or absence of language (Florisson et al, 2013; Hucthagowder et al, 2012). Apart from Peter, Matsushita, Oda, and Raskind, (2014), who described a 200 kb 2p15p16.1 deletion encompassing the entire BCL11A gene (plus 50 kb of non‐coding sequence but no other known coding or non‐coding gene) in a patient with mild intellectual disability, childhood apraxia of speech, dysarthria, and oral and motor dyspraxia, language anomalies have not been extensively studied in patients with mutations or microdeletions affecting BCL11A .…”

Section: Introductionmentioning

confidence: 99%

BCL11A frameshift mutation associated with dyspraxia and hypotonia affecting the fine, gross, oral, and speech motor systems

Soblet

Dimov

Kalckreuth

et al. 2017

American J of Med Genetics Pt A

View full text Add to dashboard Cite

We report the case of a 7‐year‐old male of Western European origin presenting with moderate intellectual disability, severe childhood apraxia of speech in the presence of oral and manual dyspraxia, and hypotonia across motor systems including the oral and speech motor systems. Exome sequencing revealed a de novo frameshift protein truncating mutation in the fourth exon of BCL11A, a gene recently demonstrated as being involved in cognition and language development. Making parallels with a previously described patient with a 200 kb 2p15p16.1 deletion encompassing the entire BCL11A gene and displaying a similar phenotype, we characterize in depth how BCL11A is involved in clinical aspects of language development and oral praxis.

show abstract

Prevalence of Pathogenic Copy Number Variation in Adults With Pediatric-Onset Epilepsy and Intellectual Disability

et al. 2017

View full text Add to dashboard Cite

IMPORTANCECopy number variation (CNV) is an important cause of neuropsychiatric disorders. Little is known about the role of CNV in adults with epilepsy and intellectual disability.OBJECTIVES To evaluate the prevalence of pathogenic CNVs and identify possible candidate CNVs and genes in patients with epilepsy and intellectual disability. DESIGN, SETTING, AND PARTICIPANTSIn this cross-sectional study, genome-wide microarray was used to evaluate a cohort of 143 adults with unexplained childhood-onset epilepsy and intellectual disability who were recruited from the Toronto Western Hospital epilepsy outpatient clinic from January 1, 2012, through December 31, 2014. The inclusion criteria were (1) pediatric seizure onset with ongoing seizure activity in adulthood, (2) intellectual disability of any degree, and (3) no structural brain abnormalities or metabolic conditions that could explain the seizures.MAIN OUTCOMES AND MEASURES DNA screening was performed using genome-wide microarray platforms. Pathogenicity of CNVs was assessed based on the American College of Medical Genetics guidelines. The Residual Variation Intolerance Score was used to evaluate genes within the identified CNVs that could play a role in each patient's phenotype. RESULTSOf the 2335 patients, 143 probands were investigated (mean [SD] age, 24.6 [10.8] years; 69 male and 74 female). Twenty-three probands (16.1%) and 4 affected relatives (2.8%) (mean [SD] age, 24.1 [6.1] years; 11 male and 16 female) presented with pathogenic or likely pathogenic CNVs (0.08-18.9 Mb). Five of the 23 probands with positive results (21.7%) had more than 1 CNV reported. Parental testing revealed de novo CNVs in 11 (47.8%), with CNVs inherited from a parent in 4 probands (17.4%). Sixteen of 23 probands (69.6%) presented with previously cataloged human genetic disorders and/or defined CNV hot spots in epilepsy. Eight nonrecurrent rare CNVs that overlapped 1 or more genes associated with intellectual disability, autism, and/or epilepsy were identified: 2p16.1-p15 duplication, 6p25.3-p25.1 duplication, 8p23.3p23.1 deletion, 9p24.3-p23 deletion, 10q11.22-q11.23 duplication, 12p13.33-13.2 duplication, 13q34 deletion, and 16p13.2 duplication. Five genes are of particular interest given their potential pathogenicity in the corresponding phenotypes and least tolerability to variation: ABAT, KIAA2022, COL4A1, CACNA1C, and SMARCA2. ABAT duplication was associated with Lennox-Gastaut syndrome and KIAA2022 deletion with Jeavons syndrome. CONCLUSIONS AND RELEVANCEThe high prevalence of pathogenic CNVs in this study highlights the importance of microarray analysis in adults with unexplained childhood-onset epilepsy and intellectual disability. Additional studies and comparison with similar cases are required to evaluate the effects of deletions and duplications that overlap specific genes.

show abstract

Brain malformations in a patient with deletion 2p16.1: A refinement of the phenotype to BCL11A

Cited by 25 publications

References 23 publications

Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis

Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis

BCL11A frameshift mutation associated with dyspraxia and hypotonia affecting the fine, gross, oral, and speech motor systems

Prevalence of Pathogenic Copy Number Variation in Adults With Pediatric-Onset Epilepsy and Intellectual Disability

Contact Info

Product

Resources

About