scholarly journals Balanced translocation t(3;18)(p13;q22.3) and points mutation in the ZNF407 gene detected in patients with both moderate non-syndromic intellectual disability and autism

2013 ◽  
Vol 1832 (3) ◽  
pp. 431-438 ◽  
Author(s):  
Cong-mian Ren ◽  
Yan Liang ◽  
Fengxiang Wei ◽  
Ya-nan Zhang ◽  
Shou-qiang Zhong ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Balanced Translocation

A Novel SETBP1 Gene Disruption by a De Novo Balanced Translocation in a Patient with Speech Impairment, Intellectual, and Behavioral Disorder

2020 ◽  
Author(s):  
Ivona Vrkić Boban ◽  
Futoshi Sekiguchi ◽  
Mirela Lozić ◽  
Noriko Miyake ◽  
Naomichi Matsumoto ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Autosomal Dominant ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Chromosome Translocation ◽  
Behavioral Disorder ◽  
Behavioral Difficulties ◽  
Speech Impairment ◽  
Balanced Translocation ◽  
Severe Intellectual Disability

AbstractBalanced chromosomal abnormalities (BCAs) can disrupt gene function resulting in disease. To date, BCA disrupting the SET binding protein 1 (SETBP1) gene has not been reported. On the other hand, de novo heterozygous variants in the highly conserved 11-bp region in SETBP1 can result in the Schinzel–Giedion syndrome. This condition is characterized by severe intellectual disability, a characteristic face, and multiple-system anomalies. Further other types of mutations involving SETBP1 are associated with a different phenotype, mental retardation, autosomal dominant 29 (MRD29), which has mild dysmorphic features, developmental delay, and behavioral disorders. Here we report a male patient who has moderate intellectual disability, mild behavioral difficulties, and severe expressive speech impairment resulting from a de novo balanced chromosome translocation, t(12;18)(q22;q12.3). By whole genome sequencing, we determined the breakpoints at the nucleotide level. The 18q12.3 breakpoint was located between exons 2 and 3 of SETBP1. Phenotypic features of our patient are compatible with those with MRD29. This is the first reported BCA disrupting SETBP1.

A Familial 14q32.32q32.33 Duplication/17p13.3 Deletion Syndrome with Facial Anomalies and Moderate Intellectual Disability

2016 ◽  
Vol 148 (4) ◽  
pp. 262-267 ◽  
Author(s):  
Chunxia He ◽  
Changhu Dong ◽  
Jingyi Li ◽  
Depin Hu ◽  
Libo Yao ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Chromosome 17 ◽  
Deletion Syndrome ◽  
Derivative Chromosome ◽  
Balanced Translocation ◽  
Moderate Intellectual Disability ◽  
Cytogenetic Aberration ◽  
Subtelomeric Rearrangement ◽  
Metopic Suture ◽  
Chromosome Regions

To our knowledge, a derivative chromosome 17 formed by a subtelomeric translocation involving chromosomes 17 and 14 has not been reported before. Here, we present the clinical and molecular cytogenetic characteristics of 2 family members with a subtelomeric rearrangement involving chromosome regions 14q32.32q32.33 and 17p13.3. The patients had moderate intellectual disability, a high forehead, a broad nasal root, downslanting palpebral fissures, epicanthal folds, retrognathia, hypertelorism, wrinkled skin over the glabella and metopic suture, and mild finger clubbing. Array CGH detected a 2.52-Mb duplication of 14q32.32q32.33 (103,805,680-106,396,479) and a 1.2-Mb deletion of 17p13.3 (87,009-1,298,869) confirmed to be pathogenic by quantitative PCR and loss of heterozygosity analysis of 17p13.3. The derivative chromosome 17 was inherited from a parental balanced translocation. To our knowledge, this cytogenetic aberration has not been described previously. The refinement of the genetic location will improve the knowledge of the genes responsible for this phenotype.

scholarly journals Inherited unbalanced translocation (4p16.3p15.32 duplication/8p23.3p23.2deletion) in the four generation pedigree with intellectual disability/developmental delay

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Dongmei Hao ◽  
Yajuan Li ◽  
Lisha Chen ◽  
Xiliang Wang ◽  
Mengxing Wang ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Intellectual Disability ◽  
Developmental Delay ◽  
Copy Number Variants ◽  
Snp Array ◽  
Normal Karyotype ◽  
Clinical Syndrome ◽  
Chromosome 8 ◽  
Fish Analysis ◽  
Balanced Translocation

AbstractChromosomal copy number variants (CNVs) are an important cause of congenital malformations and mental retardation. This study reported a large Chinese pedigree (4-generation, 76 members) with mental retardation caused by chromosome microduplication/microdeletion. There were 10 affected individuals with intellectual disability (ID), developmental delay (DD), and language delay phenotypes. SNP array analysis was performed in the proband and eight patients and found all of them had a microduplication of chromosome 4p16.3p15.2 and a microdeletion of chromosome 8p23.3p23.2. The high-resolution karyotyping analysis of the proband had unbalanced karyotype [46, XY, der(8)t(4;8)(p15.2;p23.1)mat], his mother had balanced karyotype [46, XX, t(4;8) (p15.2;p23.1)], whereas his father had normal karyotype [46,XY]. Fluorescence in situ hybridization (FISH) analysis further confirmed that the proband’s mother had a balanced translocation between the short arm terminal segment of chromosome 4 and the short arm end segment of chromosome 8, ish t(4;8)(8p + ,4q + ;4p + ,8q +). In conclusion, all the patients inherited chromosomes 8 with 4p16.3p15.2 duplication and 8p23.3p23.2 deletion from their parental balanced translocation, which might be the cause of the prevalence of intellectual disability. Meanwhile, 8p23.3p23.2 deletion, rather than 4p16.3p15.2 duplication might cause a more severe clinical syndrome.

scholarly journals A rare familial rearrangement of chromosomes 9 and 15 associated with intellectual disability: a clinical and molecular study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Natalya A. Lemskaya ◽  
Svetlana A. Romanenko ◽  
Mariia A. Rezakova ◽  
Elena A. Filimonova ◽  
Dmitry Yu. Prokopov ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Extra Chromosome ◽  
Brain Mri ◽  
Partial Trisomy ◽  
Breakpoint Region ◽  
Chromosome Anomaly ◽  
Chromosome 15 ◽  
Derivative Chromosome ◽  
Balanced Translocation ◽  
Mri Features

Abstract Background There are many reports on rearrangements occurring separately in the regions of chromosomes 9p and 15q affected in the case under study. 15q duplication syndrome is caused by the presence of at least one extra maternally derived copy of the Prader–Willi/Angelman critical region. Trisomy 9p is the fourth most frequent chromosome anomaly with a clinically recognizable syndrome often accompanied by intellectual disability. Here we report a new case of a patient with maternally derived unique complex sSMC resulting in partial trisomy of both chromosomes 9 and 15 associated with intellectual disability. Case presentation We characterise a supernumerary derivative chromosome 15: 47,XY,+der(15)t(9;15)(p21.2;q13.2), likely resulting from 3:1 malsegregation during maternal gametogenesis. Chromosomal analysis showed that a phenotypically normal mother is a carrier of balanced translocation t(9;15)(p21.1;q13.2). Her 7-year-old son showed signs of intellectual disability and a number of physical abnormalities including bilateral cryptorchidism and congenital megaureter. The child’s magnetic resonance imaging showed changes in brain volume and in structural and functional connectivity revealing phenotypic changes caused by the presence of the extra chromosome material, whereas the mother’s brain MRI was normal. Sequence analyses of the microdissected der(15) chromosome detected two breakpoint regions: HSA9:25,928,021-26,157,441 (9p21.2 band) and HSA15:30,552,104-30,765,905 (15q13.2 band). The breakpoint region on chromosome HSA9 is poor in genetic features with several areas of high homology with the breakpoint region on chromosome 15. The breakpoint region on HSA15 is located in the area of a large segmental duplication. Conclusions We discuss the case of these phenotypic and brain MRI features in light of reported signatures for 9p partial trisomy and 15 duplication syndromes and analyze how the genomic characteristics of the found breakpoint regions have contributed to the origin of the derivative chromosome. We recommend MRI for all patients with a developmental delay, especially in cases with identified rearrangements, to accumulate more information on brain phenotypes related to chromosomal syndromes.

Identification of disruptedAUTS2andEPHA6genes by array painting in a patient carrying a de novo balanced translocation t(3;7) with intellectual disability and neurodevelopment disorder

2015 ◽  
Vol 167 (12) ◽  
pp. 3031-3037 ◽  
Author(s):  
Anouck Schneider ◽  
Jacques Puechberty ◽  
Bee Ling Ng ◽  
Christine Coubes ◽  
Vincent Gatinois ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Balanced Translocation

scholarly journals A female patient with retinoblastoma and severe intellectual disability carrying an X;13 balanced translocation without rearrangement in the RB1 gene: a case report

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Makiko Tsutsumi ◽  
Hiroyoshi Hattori ◽  
Nobuhiro Akita ◽  
Naoko Maeda ◽  
Toshinobu Kubota ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Female Patient ◽  
Peripheral Blood ◽  
Regulatory Region ◽  
Translocation Chromosome ◽  
Deletion Syndrome ◽  
Balanced Translocation ◽  
Specific Pcr ◽  
Autosomal Region ◽  
Severe Intellectual Disability

Abstract Background Female carriers of a balanced X; autosome translocation generally undergo selective inactivation of the normal X chromosome. This is because inactivation of critical genes within the autosomal region of the derivative translocation chromosome would compromise cellular function. We here report a female patient with bilateral retinoblastoma and a severe intellectual disability who carries a reciprocal X-autosomal translocation. Case presentation Cytogenetic and molecular analyses, a HUMARA (Human androgen receptor) assay, and methylation specific PCR (MSP) and bisulfite sequencing were performed using peripheral blood samples from the patient. The patient’s karyotype was 46,X,t(X;13)(q28;q14.1) by G-banding analysis. Further cytogenetic analysis located the entire RB1 gene and its regulatory region on der(X) with no translocation disruption. The X-inactivation pattern in the peripheral blood was highly skewed but not completely selected. MSP and deep sequencing of bisulfite-treated DNA revealed that an extensive 13q region, including the RB1 promoter, was unusually methylated in a subset of cells. Conclusions The der(X) region harboring the RB1 gene was inactivated in a subset of somatic cells, including the retinal cells, in the patient subject which acted as the first hit in the development of her retinoblastoma. In addition, the patient’s intellectual disability may be attributable to the inactivation of the der(X), leading to a 13q deletion syndrome-like phenotype, or to an active X-linked gene on der (13) leading to Xq28 functional disomy.

scholarly journals Allelic and dosage effects of NHS in X-linked cataract and Nance–Horan syndrome: a family study and literature review

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Caroline Miller ◽  
Benjamin G. Gertsen ◽  
Audrey L. Schroeder ◽  
Chin-To Fong ◽  
M. Anwar Iqbal ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Gene Disruption ◽  
Single Gene ◽  
Horseshoe Kidney ◽  
Partial Trisomy ◽  
Primary Amenorrhea ◽  
Fish Analysis ◽  
Balanced Translocation ◽  
Partial Monosomy ◽  
Congenital Cataracts

AbstractNance–Horan syndrome (NHS) is a rare X-linked dominant disorder caused by mutation in the NHS gene on chromosome Xp22.13. (OMIM 302350). Classic NHS manifested in males is characterized by congenital cataracts, dental anomalies, dysmorphic facial features and occasionally intellectual disability. Females typically have a milder presentation. The majority of reported cases of NHS are the result of nonsense mutations and small deletions. Isolated X-linked congenital cataract is caused by non-recurrent rearrangement-associated aberrant NHS transcription. Classic NHS in females associated with gene disruption by balanced X-autosome translocation has been infrequently reported. We present a familial NHS associated with translocation t(X;19) (Xp22.13;q13.1). The proband, a 28-year-old female, presented with intellectual disability, dysmorphic features, short stature, primary amenorrhea, cleft palate, and horseshoe kidney, but no NHS phenotype. A karyotype and chromosome microarray analysis (CMA) revealed partial monosomy Xp/partial trisomy 19q with the breakpoint at Xp22.13 disrupting the NHS gene. Family history revealed congenital cataracts and glaucoma in the patient’s mother, and congenital cataracts in maternal half-sister and maternal grandmother. The same balanced translocation t(X;19) was subsequently identified in both the mother and maternal half-sister, and further clinical evaluation of the maternal half-sister made a diagnosis of NHS. This study describes the clinical implication of NHS gene disruption due to balanced X-autosome translocations as a unique mechanism causing Nance–Horan syndrome, refines dose effects of NHS on disease presentation and phenotype expressivity, and justifies consideration of karyotype and fluorescence in situ hybridization (FISH) analysis for female patients with familial NHS if single-gene analysis of NHS is negative.

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