Estimate of the prevalence of chromosome 15q11‐q13 duplications

Thomas, N. Simon; Roberts, S.E.; Browne, C. Elliot

doi:10.1002/ajmg.a.20140

Cited by 11 publications

(8 citation statements)

References 10 publications

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“…The chromosomal region 15q11-q13 is deleted in the majority of Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients [Ledbetter et al, 1981;Magenis et al, 1990], whereas duplications of this region are associated with a variety of phenotypes, including apparently normal, AS, PWS, and an abnormal phenotype not resembling either AS or PWS [Clayton-Smith et al, 1993;Bundey et al, 1994]. The prevalence of 15q11-q13 duplications is approximately 1 in 600 among patients with developmental delay (DD) [Browne et al, 1997;Thomas et al, 2003] and 2 in 100 among autistic patients [Schroer et al, 1998]. …”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

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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“…The frequency of 15q11-q13 abnormalities is 0.5 to 3% making them the most common autosomal cytogenetic abnormality in autistic disorder [Browne et al, 1997;Cook et al, 1997;Schroer et al, 1998;Bolton et al, 2001;Borgatti et al, 2001;Roberts et al, 2002Roberts et al, , 2003Thomas et al, 2002]. Most of these abnormalities are of maternal origin suggesting that an imprinted gene in the region plays a role [Cook et al, 1997;Schroer et al, 1998;Bolton et al, 2001].…”

Section: Introductionmentioning

confidence: 99%

Array‐based comparative genomic hybridization analysis of recurrent chromosome 15q rearrangements

Sahoo

Shaw

Young

et al. 2005

American J of Med Genetics Pt A

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Genomic rearrangements of chromosome 15q11-q13 cause diverse phenotypes including autism, Prader-Willi syndrome (PWS), and Angelman syndrome (AS). This region is subject to genomic imprinting and characterized by complex combinations of low copy repeat elements. Prader-Willi and Angelman syndrome are caused primarily by 15q11-13 deletions of paternal and maternal origin, respectively. Autism is seen with maternal, but not paternal, interstitial duplications. Isodicentric 15q, most often of maternal origin, is associated with a complex phenotype often including autistic features. Limitations of conventional cytogenetic tests preclude a detailed analysis in most patients with 15q rearrangements. We have developed a microarray for comparative genomic hybridization utilizing 106 genomic clones from chromosome 15q to characterize this region. The array accurately localized all breakpoints associated with gains or losses on 15q. The results confirmed the location of the common breakpoints associated with interstitial deletions and duplications. The majority of idic(15q) chromosomes are comprised of symmetrical arms with four copies of the breakpoint 1 to breakpoint 5 region. Patients with less common breakpoints that are not distinguished by routine cytogenetic methods were more accurately characterized by array analysis. This microarray provides a detailed characterization for chromosomal abnormalities involving 15q11-q14 and is useful for more precise genotype-phenotype correlations for autism, PWS, AS, and idic(15) syndrome.

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“…Duplications of the Prader Willi/Angelman syndrome critical region (PWS/ASCR) on proximal chromosome 15q occur with an estimated frequency of 1:600 children presenting with developmental delay (Thomas et al 2003). Most often these occur through the generation of a supernumerary derivative chromosome 15 that carries two copies of the satellited short arm and centromere and are therefore termed isodicentric, idic(15), although only one centromere is functional (Schwartz and Depinet 1996), or an inverted duplication 15 chromosome (Schreck et al 1977).…”

Section: Introductionmentioning

confidence: 99%

Supernumerary tricentric derivative chromosome 15 in two boys with intractable epilepsy: another mechanism for partial hexasomy

et al. 2004

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Rearrangements of chromosome 15q, including isodicentric 15 chromosomes and interstitial duplications and triplications, have been previously reported in association with autism spectrum disorders. We have identified two boys with exceptionally large der(15) chromosomes that are tricentric and contain four copies of the proximal long arm, including the Prader Willi/Angelman critical region, and leading to hexasomy of the involved segment. Biallelic inheritance of maternal alleles and methylation analysis indicate that the markers are maternally derived. Clinical assessment of the boys indicated severe cognitive impairment associated with marked delays in gross and fine motor skills. Social and language deficits were present in both, although the severity of the mental retardation precluded diagnosis of autism (both were considered to have pervasive developmental disorder-not otherwise specified). Neurologic manifestations included infantile spasms evolving into intractable early-onset myoclonic seizures, psychomotor regression, and profound diffuse hypotonia. These patients represent the most severe end of the spectrum of phenotypes associated with segmental aneuploidy for chromosome 15q11-q13.

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Estimate of the prevalence of chromosome 15q11‐q13 duplications

Cited by 11 publications

References 10 publications

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

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

Array‐based comparative genomic hybridization analysis of recurrent chromosome 15q rearrangements

Supernumerary tricentric derivative chromosome 15 in two boys with intractable epilepsy: another mechanism for partial hexasomy

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