Triplication of 15q11-q13 with inv dup(15) in a female with developmental delay.

Long, Fiona; Duckett, D P; Billam, L J; Williams, David; Crolla, John A.

doi:10.1136/jmg.35.5.425

Cited by 45 publications

(51 citation statements)

References 12 publications

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“…For example, copynumber variants resulting from the reciprocal deletion and duplication products of nonallelic recombination are associated with dozens of recurrent human disorders (Stankiewicz and Lupski 2002;Shaw and Lupski 2004;Sharp et al 2005;Turner et al 2008;Abyzov et al 2015;Martin et al 2015). These include hereditary neuropathy with liability to pressure palsies and Charcot-Marie -Tooth disease type 1A (Chance et al 1994), Prader-Willi syndrome/ Angelman syndrome and 15q11q13 duplication (Long et al 1998), velocardiofacial syndrome and dup22(q11.2q11.2) (Edelmann et al 1999a), Smith -Magenis syndrome and Potocki -Lupski syndrome (Potocki et al 2000), and Williams -Beuren syndrome and dup7 (q11.23) (Somerville et al 2005). Other rearrangements, such as translocations, may create gene imbalances that are incompatible with fetal development, as seen for most aneuploidies.…”

Section: Meiotic Recombination and Genomic Disordersmentioning

confidence: 99%

Meiotic Recombination: The Essence of Heredity

Hunter

2015

Cold Spring Harb Perspect Biol

696

869

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The study of homologous recombination has its historical roots in meiosis. In this context, recombination occurs as a programmed event that culminates in the formation of crossovers, which are essential for accurate chromosome segregation and create new combinations of parental alleles. Thus, meiotic recombination underlies both the independent assortment of parental chromosomes and genetic linkage. This review highlights the features of meiotic recombination that distinguish it from recombinational repair in somatic cells, and how the molecular processes of meiotic recombination are embedded and interdependent with the chromosome structures that characterize meiotic prophase. A more in-depth review presents our understanding of how crossover and noncrossover pathways of meiotic recombination are differentiated and regulated. The final section of this review summarizes the studies that have defined defective recombination as a leading cause of pregnancy loss and congenital disease in humans. MEIOSIS AND THE ROOTS OF RECOMBINATION RESEARCHT he concept of recombination emerged during the early 20th century, following the post-Mendel era of heredity research. Thomas Hunt Morgan's formal theory of gene linkage and crossing-over (Morgan 1913) was a synthesis of three key concepts: "the chromosome theory of inheritance," imparted by Wilhelm Roux, Walther Flemming, Theodor Boveri, and Walter Sutton; "gene linkage," an exception to Mendel's law of independent assortment, first reported by Carl Correns; and the "chiasmatype theory," derived from Frans Janssens' cytological observations of meiotic chromosomes. The first proof of the crossover theory came from Harriet Creighton and Barbara McClintock (Creighton and McClintock 1931), who were able to correlate cytological and genetic exchanges in maize.Experiments aimed at understanding the mechanism of meiotic recombination became dominated by fungal genetics because of the huge advantage afforded by being able to recover all four meiotic products. These elegant studies culminated in four key concepts that formed the foundation of molecular models of recombination: gene conversion, an exception to Mendel's principle of segregation, signaled a local nonreciprocal transfer of genetic information (Winkler 1930;Lindergren 1953;Mitchell 1955); postmeiotic segregation (PMS) indicated the presence of heteroduplex DNA (Olive 1959;Kitani et al. 1962) (Lissouba and Rizet 1960;Murray 1960); and the strong correlation between gene conversion/ PMS events and crossing-over led to the proposal that these processes were mechanistically linked (Kitani et al. 1962;Perkins 1962;Whitehouse 1963). MOLECULAR MODELS OF MEIOTIC RECOMBINATIONHolliday's classic model reconciled gene conversion, PMS, and crossing-over into a single mechanism with the key features of hybrid (heteroduplex) DNA formed via strand exchange, mismatch correction of hybrid DNA to yield gene conversion, and a four-way exchange junction that could be resolved to yield either crossover or noncrossover duplex products (Holliday...

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Section: Meiotic Recombination and Genomic Disordersmentioning

confidence: 99%

Meiotic Recombination: The Essence of Heredity

Hunter

2015

Cold Spring Harb Perspect Biol

696

869

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“…Interstitial triplications of 15q11-q13, which result in the tetrasomy of this region, are rare, with only 11 cases reported in the literature [Pettigrew et al, 1987;Clayton-Smith et al, 1993;Holowinsky et al, 1993;Schinzel et al, 1994;Crawford et al, 1995;Cassidy et al, 1996;Chadwick et al, 1996;Long et al, 1998;Reddy and Logan, 2000;Ungaro et al, 2001;Vialard et al, 2003]. Although this small number precludes a precise definition of the associated phenotypes, particularly in cases of paternal origin [Pettigrew et al, 1987;Cassidy et al, 1996;Ungaro et al, 2001], the clinical presentations generally resemble those of patients with tetrasomy of the same region due to an inv dup(15) marker chromosome: normal growth, absent, or very mild craniofacial dysmorphism, hypotonia, epilepsy refractory to therapy, severe to profound intellectual disability (ID), and variable reports of autistic behavior [Robinson et al, 1993;Cheng et al, 1994;Leana-Cox et al,1994;Crolla et al, 1995;Mignon et al, 1996].…”

Section: Introductionmentioning

confidence: 96%

Complex de novo chromosomal rearrangement at 15q11–q13 involving an intrachromosomal triplication in a patient with a severe neuropsychological phenotype: Clinical report and review of the literature

Castronovo

Crippa

Bestetti

et al. 2014

American J of Med Genetics Pt A

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Interstitial triplications of 15q11-q13, leading to tetrasomy of the involved region, are very rare, with only 11 cases reported to date. Their pathogenicity is independent of the parental origin of the rearranged chromosome. The associated phenotype resembles, but is less severe, than that of patients bearing inv dup(15) marker chromosomes. Here, we describe a boy of 3 years and 9 months of age who exhibited very mild craniofacial dysmorphism (arched eyebrows, hypertelorism, and a wide mouth), developmental delay, generalized hypotonia, ataxic gait, severe intellectual disability, and autism. Array comparative genomic hybridization (CGH) analysis identified a heterozygous duplication of 1.1 Mb at 15q11.2 (between low-copy repeats BP1 and BP2), and a heterozygous triplication of 6.8 Mb at 15q11.2-q13.1 (BP2-BP4). Both acquisitions were de novo and contiguous. Microsatellite polymorphism analysis revealed the maternal origin of the triplication and the involvement of both maternal chromosomes 15. Furthermore, fluorescence in situ hybridization (FISH) analysis using BAC clones revealed that the rearrangement was complex, containing three differently sized tandem repeats of which the middle one was inverted. Our study confirms and extends the model proposed to explain the formation of intrachromosomal triplications through recombination events between non-allelic duplicons. The comparison of the proband's clinical presentation with those of previously described cases attests the existence of endophenotypes due to the parental origin of the 15q11-q13 triplicated segment and suggests a timetable for achievement of developmental milestones, thereby contributing to improved genotype-phenotype correlations.

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“…Only a few cases of intrachromosomal triplication have been described [Berry et al, 1990;Holowinsky et al, 1993;Schinzel et al, 1994;Cassidy et al, 1996;Rauch et al, 1996; Devriendt, 1998, personal communication;Harrison et al, 1998;Long et al, 1998;Rivera et al, 1998] These involved chromosomes 2, 5, 7, 10, 15, and 16. We describe the clinical manifestations of our patient, compare them with other cases of tetrasomy 9p, and discuss probable mechanisms causing this chromosomal aberration.…”

Section: Introductionmentioning

confidence: 96%

Tetrasomy 9p due to an intrachromosomal triplication of 9p13-p22

Verheij

Bouman

Lingen³

et al. 1999

Am. J. Med. Genet.

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To date, approximately 30 patients have been described with a tetrasomy 9p, all being caused by the presence of an isochromosome 9p. We now report on a 3-year-old boy with a de novo intrachromosomal triplication of 9p13-p22, resulting in partial tetrasomy 9p. We compared his phenotype with cases of tetrasomy 9p caused by the presence of an extra isochromosome 9p. He has facial anomalies similar to those of cases of tetrasomy 9p, central nervous system abnormalities, and severe psychomotor retardation but no other major congenital anomalies. Fluorescence in situ hybridization with region-specific probes showed that the middle repeat of the triplicated part is inverted. Microsatellite analysis demonstrated an involvement of both paternal chromosome 9 homologues in the triplication. This is compatible with either unequal crossing over of three of the four chromatids in paternal meiosis I or with a double crossing over in meiosis I and II (or an early mitotic division).

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Triplication of 15q11-q13 with inv dup(15) in a female with developmental delay.

Cited by 45 publications

References 12 publications

Meiotic Recombination: The Essence of Heredity

Meiotic Recombination: The Essence of Heredity

Complex de novo chromosomal rearrangement at 15q11–q13 involving an intrachromosomal triplication in a patient with a severe neuropsychological phenotype: Clinical report and review of the literature

Tetrasomy 9p due to an intrachromosomal triplication of 9p13-p22

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