Microdeletion and microduplication 17q21.31 plus an additional CNV, in patients with intellectual disability, identified by array-CGH

Kitsiou-Tzeli, Sophia; Frysira, Helen; Γιαννίκου, Κρινιώ; Syrmou, Areti; Kosma, Konstantina; Kakourou, Georgia; Leze, Eleni; Sofocleous, Christalena; Kanavakis, Emmanuel; Tzetis, Maria

doi:10.1016/j.gene.2011.10.023

Cited by 29 publications

(24 citation statements)

References 22 publications

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“…13,18,20,22,30 In our cohort, we observed behavioural problems in 57% of cases. These problems included autism/autistic traits, ADHD/attention deficit/ hyperactivity, shyness, anxiety/phobias, impulsive and stereotypic behaviour, psychosis, and depression.…”

Section: Neuropsychological Disorderssupporting

confidence: 48%

“…A search of the medical literature identified 23 articles describing the clinical features of 81 patients with KdVS. [1][2][3][4][5]13,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] …”

Section: Methodsmentioning

confidence: 99%

“…13,18,22 Ectodermal abnormalities Ectodermal abnormalities were present in 67% of our cases and have previously been described. 13,18,22,24,26,30 Skin involvement included, among others, multiple nevi, depigmentosa, hyperkeratosis, eczema, keratosis pilaris, café-au-lait maculae, ichthyosis vulgaris, acne vulgaris, piezogenic papules, and hemangiomas. Importantly, case 17 developed melanoma at 9 years of age.…”

Section: Cardiovascular Defectsmentioning

confidence: 99%

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The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

et al. 2015

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The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.

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Section: Neuropsychological Disorderssupporting

confidence: 48%

Section: Methodsmentioning

confidence: 99%

Section: Cardiovascular Defectsmentioning

confidence: 99%

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The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

et al. 2015

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“…In addition, we compared the effectiveness of aCGH with conventional methods in Saudi Arabian patients. We reported a number of congenital malformations in these patients which were in agreement with other studies [Goldberg et al, 1993;Leana-Cox et al, 1996;Ryan et al, 1997;Kitsiou-Tzeli et al, 2012]. Our results show that G-banding detected this deletion in only 1 patient out of 30 (3.3%) ( Table 2 ).…”

Section: Discussionsupporting

confidence: 92%

Use of Array Comparative Genomic Hybridization for the Diagnosis of DiGeorge Syndrome in Saudi Arabian Population

Bahamat

Assidi

Lary³

et al. 2018

Cytogenet Genome Res

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DiGeorge syndrome (DGS) is a genetic disorder known as a clinically variable syndrome with over 180 associated phenotypic features. It is caused by a common human deletion in the 22q11.2 chromosomal region and currently is affecting approximately 1 in 4,000 individuals. Despite the prevalence of inherited diseases mainly due to consanguineous marriages, the current diagnosis of DGS in Saudi Arabia is mainly based on conventional high-resolution chromosome banding (karyotyping) and FISH techniques. However, advanced genome-wide studies for detecting microdeletions or duplications across the whole genome are needed. The aim of this study is to implement and use aCGH technology in clinical diagnosis of the 22q11.2 deletion in Saudi Arabian DGS patients and to confirm its effectiveness compared to conventional FISH and chromosome banding techniques. Thirty suspected DGS patients were assessed for chromosome 22q11.2 deletion using high-resolution G-banding, FISH, and aCGH. The aCGH results were compared with those obtained by the other 2 cytogenetic techniques. G-banding detected the 22q11.2 deletion in only 1 patient in the cohort. Moreover, it detected additional chromosomal aberrations in 3 other patients. Using FISH, allowed for detection of the 22q11.2 deletion in 2 out of 30 patients. Interestingly, the use of aCGH technique showed deletions in the chromosome 22q11.2 region in 8 patients, indicating a 4-fold increase in diagnostic detection capacity compared to FISH. Our results show the effectiveness of aCGH to overcome the limitations of FISH and G-banding in terms of diagnostic yield and allow whole genome screening and detection of a larger number of deletions and/or duplications in Saudi Arabian DGS patients. Except for balanced translocations and inversions, our data demonstrate the suitability of aCGH in the diagnostics of submicroscopic deletion syndromes such as DGS and most chromosomal aberrations or complex abnormalities scattered throughout the human genome. Our results recommend the implementation of aCGH in clinical genomic testing in Saudi Arabia to improve the diagnostic capabilities of health services while maintaining the use of conventional cytogenetic techniques for subsequent validation or for specific and known aberrations whenever required.

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“…48,[50][51][52] The H1 family of haplotypes has been associated with increased risk for late-life tauopathies, diseases marked by the accumulation of MAPT neurofibrillary tangles in nerve cells, such as sporadic frontotemporal dementia, 53 Alzheimer's disease, 54 Parkinson's disease 55 and progressive supranuclear palsy. 48 By contrast, the H2 haplotype has been associated with developmental delay and learning difficulties, 51,[56][57][58] as well as reduced intracranial volume. 52 Consistent with these latter observations, our data suggest alleles corresponding to the H2 haplotype are associated with worse cognitive performance.…”

mentioning

confidence: 99%

Gwas Meta-Analysis Reveals Novel Loci And Genetic Correlates For General Cognitive Function: A Report From The Cogent Consortium

Lencz

2017

European Neuropsychopharmacology

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The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾ 1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P o 5 × 10 − 8 ). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e. = 0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional Molecular Psychiatry (2017) 22, 336-345 www.nature.com/mp significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.

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Microdeletion and microduplication 17q21.31 plus an additional CNV, in patients with intellectual disability, identified by array-CGH

Cited by 29 publications

References 22 publications

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

Use of Array Comparative Genomic Hybridization for the Diagnosis of DiGeorge Syndrome in Saudi Arabian Population

Gwas Meta-Analysis Reveals Novel Loci And Genetic Correlates For General Cognitive Function: A Report From The Cogent Consortium

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