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.

Two-Generation Transmission of Trisomy 18p: Prenatal Diagnosis in a Woman with Mild Intellectual Disability

2019 ◽  
Vol 157 (4) ◽  
pp. 220-226
Author(s):  
Yang Yu ◽  
Yuting Jiang ◽  
Xiaonan Hu ◽  
Hongguo Zhang ◽  
Ruizhi Liu ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Prenatal Diagnosis ◽  
Prenatal Testing ◽  
Unknown Origin ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Chromosome 15 ◽  
Derivative Chromosome ◽  
Mild Intellectual Disability ◽  
Trisomy 18P

Trisomy 18p is a rarely observed chromosomal aberration. Only 31 cases have previously been described in the literature. Trisomy 18p is associated with mild to moderate phenotypic anomalies and intellectual disability. Here, we report on a pregnant woman in whom noninvasive prenatal testing indicated a high risk of fetal trisomy 18. Prenatal diagnosis and karyotyping of the parents were performed and demonstrated that both the mother and the fetus had a derivative chromosome 15 with a segment of unknown origin. Chromosomal microarray analysis and FISH revealed a 14.9-Mb duplication of 18p and detected 3 centromeres of chromosome 18. To our knowledge, this is the first study reporting trisomy 18p due to an unbalanced translocation of 18p onto chromosome 15q showing 2-generation transmission. The results suggest that trisomy 18p can be considered a euchromatic variant.

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 Clinical Expression of an Inherited Unbalanced Translocation in Chromosome 6

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Bani Bandana Ganguly ◽  
Vijay Kadam ◽  
Nitin N. Kadam
Keyword(s):  
Chromosomal Rearrangements ◽  
Phenotypic Expression ◽  
Partial Trisomy ◽  
Derivative Chromosome ◽  
Chromosome 6 ◽  
Clinical Expression ◽  
Balanced Translocation ◽  
Nasal Bridge ◽  
Flat Nasal Bridge ◽  
Chromosomal Alteration

Unbalanced chromosomal rearrangements are not common; however, they have a significant clinical expression. The parental balanced translocation produces unbalanced chromosome, which is transmitted to next generation through fertilization of gametes carrying the derivative chromosome. The carriers of balanced rearrangements mostly do not have recognizable phenotypic expression. We report a family comprising of healthy and non-consanguineous young parents and their preemie newborn severely affected with congenital anomalies and systemic disorders. Conventional Gbanding analysis of somatic chromosomes identified a balanced translocation, t(6;10)(p23;q24), in mother and an unbalanced rearrangement, der(6)t(6:10)(p23;q24)mat, in the child. The child has inherited a derivative chromosome 6 with partial deletion of 6(p23-pter) and partial trisomy 10(q24-qter), which has resulted in fusion of genes of two different chromosomes. The prominent phenotypic features of del(6p), including high forehead, flat nasal bridge, agenesis of left ear, atrial septal defect (ASD), craniosynostosis, and growth retardation, are overlapping with specific Axenfeld-Reiger-, Larsen-, and Ritscher-Sinzel/3-C syndromes, however, lacking in ocular anomalies, skeletal laxity, or cerebellar malformation. Therefore, this paper rules out the isolated effect of del(6p23) or trisomy 10(q24) on distinct previously reported syndromes and proposes the combined effect of unbalanced chromosomal alteration.

scholarly journals Prenatal ultrasonographic manifestations of partial trisomy 12q(12q24.2→qter) and partial monosomy 2q (2q37.3→qter)

2020 ◽  
Vol 77 (7) ◽  
pp. 754-757
Author(s):  
Ivana Joksic ◽  
Thomas Liehr ◽  
Mina Toljic ◽  
Natasa Karadzov-Orlic ◽  
Zagorka Milovanovic ◽  
...  
Keyword(s):  
Umbilical Artery ◽  
Partial Trisomy ◽  
First Trimester ◽  
Derivative Chromosome ◽  
Chromosome 2 ◽  
Balanced Translocation ◽  
Single Umbilical Artery ◽  
Partial Monosomy ◽  
Cardiac Ventricle ◽  
Cytogenetic Analyses

Introduction. Partial trisomy of chromosome 12 long arm is rare condition with significant clinical impact and is usually diagnosed postnatally. Case report. We present prenatal sonographic findings and molecular cytogenetic characterization of partial trisomy 12q and partial monosomy 2q in two consecutive pregnancies of a healthy non-consanguineous couple. A 35-year-old pregnant woman G3P1A1 was referred to genetic counseling due to sonographic anomalies detected in the fetus. First trimester ultrasound examination revealed hyperechogenic focus in the left cardiac ventricle, single umbilical artery, hyperechogenic bowel and unilateral clubfoot with knee joint ankylosis. Previous pregnancy of the couple was terminated at 26th gestation weeks due to multiple fetal anomalies: bilateral ventriculomegaly, corpus callosum hypoplasia, single umbilical artery and clubfoot. In G3P1A1, amniocentesis was performed and cytogenetic analyses revealed a derivative chromosome 2. Subsequent cytogenetic analyses of parental lymphocytes showed that paternal karyotype was normal, while maternal karyotype showed a der(2). Metaphase fluorescence in situ hybridization (FISH) studies demonstrated partial trisomy 12q24.2?12qter and partial monosomy 2q37.3?2qter in the fetus, resulting from an unbalanced segregation of a maternal balanced translocation t(2;12)(q37.3;q24.2). To date, this is the first such prenatally detected case. Literature search revealed three more cases of prenatally detected partial trisomy 12q and anomalies described were consistent with ones detected in present case. Our findings contribute to further clinical delineation of partial trisomy 12q. Conclusion. Prenatal detection of single umbilical artery, clubfoot, arthogryposis and ventriculomegaly should alert suspicion to chromosome 12q aberrations.

scholarly journals Fatal Outcome in a Newborn Calf Associated with Partial Trisomy 25q and Partial Monosomy 11q, 60,XX,der(11)t(11;25)(q11;q14∼21)

2015 ◽  
Vol 146 (3) ◽  
pp. 222-229 ◽  
Author(s):  
Alessandra Iannuzzi ◽  
Viviana Genualdo ◽  
Angela Perucatti ◽  
Alfredo Pauciullo ◽  
Giovanna Varricchio ◽  
...  
Keyword(s):  
Chromosomal Aberration ◽  
Case Reports ◽  
Fatal Outcome ◽  
Partial Trisomy ◽  
Fish Analysis ◽  
Derivative Chromosome ◽  
Chromosome 11 ◽  
Balanced Translocation ◽  
Partial Monosomy ◽  
Cytogenetic Investigation

A newborn calf of the Agerolese cattle breed underwent clinical cytogenetic investigation because of hyperflexion of the forelimbs, red eyes and the inability to stand. Anamnesis revealed that the mother, phenotypically normal, carried a chromosomal aberration. The newborn died after 2 weeks, and no remarkable alterations were found by the veterinarian on postmortem examination. The mother was a carrier of a reciprocal balanced translocation rcp(11;25)(q11,q14∼21) detected after a cytogenetic investigation in 2011; however, the analysis of the newborn revealed a different chromosomal aberration with partial trisomy of chromosome 25 and partial monosomy of chromosome 11. In fact, the results showed both chromosomes 25, one chromosome 11 and only one long derivative chromosome (der11). FISH analysis, performed using BAC clones, confirmed the chromosomes and their regions involved. Finally, both the localization of the breakpoints on band q11 (centromere) of chromosome 11 and band q14-21 of chromosome 25, and the complete loss of the der25 identified the aberration as an unbalanced translocation 60,XX,der(11)t(11;25)(q11;q14∼21). A comparison with human chromosomes was also performed to search for similarities and possible genes involved in order to study their effects, thus extending the knowledge of these aberrations by case reports.

scholarly journals A Case of Partial Trisomy of 10q and Partial Monosomy of 6p Resulting from Maternal t(6;10) (p23;q24)

2021 ◽  
Author(s):  
Anjali Satyen Sabnis ◽  
Anurita S Pais ◽  
Gauri Pradhan
Keyword(s):  
Chromosomal Aberrations ◽  
Genetic Material ◽  
Partial Trisomy ◽  
Derivative Chromosome ◽  
Chromosome 6 ◽  
Balanced Translocation ◽  
Partial Monosomy ◽  
Current Case ◽  
Long Time ◽  
Future Pregnancy

Chromosomal analysis is practiced routinely since long time in congenital malformations to find out structural and or numerical chromosomal aberrations. Translocation is one of the structural chromosomal aberrations where exchange of genetic material between the chromosomes is seen because of two breakpoints. On the basis of involvement of type of chromosome, two different types of translocation are defined. A case of two-year-old girl child with the history of developmental delay, generalised hypotonia and recurrent infections was reported whose cytogenetic analysis showed additional genetic material on ‘p’ arm of one chromosome 6. To find out the additional genetic material, parental chromosomal study was done which revealed balanced translocation between ‘q’ arm of chromosome 10 and ‘p’ arm of chromosome 6 and normal chromosomal pattern in father. Balanced translocation in mother gave rise to formation of derivative chromosome 6 which was transmitted to daughter causing partial trisomy of 10q and partial monosomy of 6p. This gain and loss of genetic material could be the cause of phenotypic features. In the current case, karyotyping was an investigation of choice and offering genetic counselling regarding prenatal diagnosis in future pregnancy was a thoughtful step.

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.

scholarly journals Hemochromatosis Mutations, Brain Iron Imaging, and Dementia in the UK Biobank Cohort

2021 ◽  
pp. 1-9
Author(s):  
Janice L. Atkins ◽  
Luke C. Pilling ◽  
Christine J. Heales ◽  
Sharon Savage ◽  
Chia-Ling Kuo ◽  
...  
Keyword(s):  
Iron Reduction ◽  
Brain Mri ◽  
European Ancestry ◽  
Uk Biobank ◽  
Brain Iron ◽  
Mri Features ◽  
Incident Dementia ◽  
Hfe Mutations ◽  
The Uk

Background: Brain iron deposition occurs in dementia. In European ancestry populations, the HFE p.C282Y variant can cause iron overload and hemochromatosis, mostly in homozygous males. Objective: To estimated p.C282Y associations with brain MRI features plus incident dementia diagnoses during follow-up in a large community cohort. Methods: UK Biobank participants with follow-up hospitalization records (mean 10.5 years). MRI in 206 p.C282Y homozygotes versus 23,349 without variants, including T2 * measures (lower values indicating more iron). Results: European ancestry participants included 2,890 p.C282Y homozygotes. Male p.C282Y homozygotes had lower T2 * measures in areas including the putamen, thalamus, and hippocampus, compared to no HFE mutations. Incident dementia was more common in p.C282Y homozygous men (Hazard Ratio HR = 1.83; 95% CI 1.23 to 2.72, p = 0.003), as was delirium. There were no associations in homozygote women or in heterozygotes. Conclusion: Studies are needed of whether early iron reduction prevents or slows related brain pathologies in male HFE p.C282Y homozygotes.

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