Subcortical white matter abnormalities because of previously undescribed de-novo 14q12–q13.1 triplication

Rea, Gillian; Stallings, Ray L.; Mullarkey, M.; McKinstry, C. Steven; McManus, D.; Morrison, Patrick J.

doi:10.1097/mcd.0b013e32835f7465

Cited by 3 publications

(2 citation statements)

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“…Genomic triplications are rare unbalanced chromosomal aberrations with variable clinical effects. [7][8][9][10] The association of triplication and segmental uniparental isodisomy (isoUPD) has been reported in only one single case. 8 Deciphering the mechanism of triplications has remained challenging because of the rarity of the events and the difficulty in defining the breakpoints with accuracy.…”

Section: Introductionmentioning

confidence: 99%

Concurrent triplication and uniparental isodisomy: evidence for microhomology-mediated break-induced replication model for genomic rearrangements

et al. 2014

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Whole-genome oligonucleotide single-nucleotide polymorphism (oligo-SNP) arrays enable simultaneous interrogation of copy number variations (CNVs), copy neutral regions of homozygosity (ROH) and uniparental disomy (UPD). Structural variation in the human genome contributes significantly to genetic variation, and often has deleterious effects leading to disease causation. Co-occurrence of CNV and regions of allelic homozygosity in tandem involving the same chromosomal arm are extremely rare. Replication-based mechanisms such as microhomology-mediated break-induced replication (MMBIR) are recent models predicted to induce structural rearrangements and gene dosage aberrations; however, supportive evidence in humans for oneended DNA break repair coupled with MMBIR giving rise to interstitial copy number gains and distal loss of heterozygosity has not been documented. We report on the identification and characterization of two cases with interstitial triplication followed by uniparental isodisomy (isoUPD) for remainder of the chromosomal arm. Case 1 has a triplication at 9q21.11-q21.33 and segmental paternal isoUPD for 9q21.33-qter, and presented with citrullinemia with a homozygous mutation in the argininosuccinate synthetase gene (ASS1 at 9q34.1). Case 2 has a triplication at 22q12.1-q12.2 and segmental maternal isoUPD 22q12.2-qter, and presented with hearing loss, mild dysmorphic features and bilateral iris coloboma. Interstitial triplication coupled with distal segmental isoUPD is a novel finding that provides human evidence for one-ended DNA break and replication-mediated repair. Both copy number gains and isoUPD may contribute to the phenotype. Significantly, these cases represent the first detailed genomic analysis that provides support for a MMBIR mechanism inducing copy number gains and segmental isoUPD in tandem.

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Section: Introductionmentioning

confidence: 99%

Concurrent triplication and uniparental isodisomy: evidence for microhomology-mediated break-induced replication model for genomic rearrangements

et al. 2014

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“…Chromosome 18q deletion syndrome (MIM#601808) is the most common and is consistently associated with WMAs 25,26 . Other rare microdeletion/duplication syndromes with WMAs include 6p25 microdeletion, 27‐29 3p21.31 deletion, 30‐32 14q12‐q13.1 triplication, 33 5q14.3 deletion, 34 11q14.3 deletion, 35,36 11q24 deletion, 37 17p13.3 deletion, 38‐41 and 22q11.2q13 duplication 42 Supplementary Table S2. provides the clinical and radiological findings associated with these disorders.…”

Section: Etiologymentioning

confidence: 99%

Genetic disorders with central nervous system white matter abnormalities: An update

et al. 2020

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Several genetic disorders have variable degree of central nervous system white matter abnormalities. We retrieved and reviewed 422 genetic conditions with prominent and consistent involvement of white matter from the literature. We herein describe the current definitions, classification systems, clinical spectrum, neuroimaging findings, genomics, and molecular mechanisms of these conditions. Though diagnosis for most of these disorders relies mainly on genomic tests, specifically exome sequencing, we collate several clinical and neuroimaging findings still relevant in diagnosis of clinically recognizable disorders. We also review the current understanding of pathophysiology and therapeutics of these disorders.

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Prenatal central nervous system anomaly with skeletal dysplasia associated with a de novo interstitial tandem triplication of chromosome 14

Hall¹,

Mackie

Williams

et al. 2016

Journal of Obstetrics and Gynaecology

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Subcortical white matter abnormalities because of previously undescribed de-novo 14q12–q13.1 triplication

Cited by 3 publications

References 0 publications

Concurrent triplication and uniparental isodisomy: evidence for microhomology-mediated break-induced replication model for genomic rearrangements

Concurrent triplication and uniparental isodisomy: evidence for microhomology-mediated break-induced replication model for genomic rearrangements

Genetic disorders with central nervous system white matter abnormalities: An update

Prenatal central nervous system anomaly with skeletal dysplasia associated with a de novo interstitial tandem triplication of chromosome 14

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