Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11‐q13

Abstract

We present clinical data on 33 subjects with additional copies of the Prader-Willi-Angelman critical region (PWACR) contained in a supernumerary marker chromosome (SMC). Twenty-three subjects had a typical large non-mosaic SMC(15) containing two copies of the PWACR. They showed a variable but generally severe phenotype of learning disability and autism, with seizures in approximately two-thirds. The other 10 differed from this typical pattern in respect of mosaicism, variation in copy number, or arrangement of the PWACR within the SMC or number of SMC per cell. Clinical severity increased with the number of additional copies of the PWACR and decreased with mosaicism for a normal cell line. There was a trend for a larger number of seizures to be associated with more severe learning disability. Three subjects with interstitial triplications of 15q11-q13 showed a range of phenotypes similar to those of the typical large SMC(15). All additional copies of the PWACR in this series were maternally-derived. FISH and molecular data localizing the breakpoints of the rearrangements have been previously published or are included in this report. No correlations were found between specific clinical features and variations in breakpoints proximal and distal to the PWACR.

A survey of seizures and current treatments in 15q duplication syndrome

“…Perhaps the most common CNV in autism are proximal duplications of the long arm of chromosome 15 (15q) due to the presence of low copy repeats, which make this region susceptible to chromosomal rearrangement. 1,2 There are five common breakpoints (BP1-BP5) in the 15q11.2-q13 region, which are at the boundaries of both deletions and duplications of chromosomal regions. Deletions result in either Angelman syndrome (AS) or Prader-Willi syndrome (PWS), depending on the parent-of-origin of the affected allele containing the PWS/AS critical region (PWACR) located between BP2-BP3.…”

“…Parent-of-origin gene dosing appears to influence phenotype in idic (15); maternally inherited or derived interstitial duplications are associated with increased autism risk. 1,[10][11][12][13] Idic(15) chromosomes that include the BP2-BP3 region are virtually all maternally derived. Large maternally derived partial hexosomy for 15q11.2-q13 in two boys with intractable epilepsy further suggests that increased dosage of maternally expressed genes negatively impacts the idic(15) phenotype.…”

Molecular Cytogenetic Characterization of Two Cases with de novo Small Mosaic Supernumerary Marker Chromosomes Derived from Chromosome 16: Towards a Genotype/Phenotype Correlation

“…Indeed, the individuals carrying an sSMC show a wide range of clinical variability, which may be related to the different sizes of the sSMC, the presence and/or absence of euchromatic material, the degree of mosaicism and/or uniparental disomy (UPD) [Liehr et al, 2006]. sSMC have been described from all chromosomes although most of them are derivatives of acrocentric chromosomes [Liehr et al, 2004[Liehr et al, , 2006 and approximately 30% are inherited [Dennis et al, 2006;Liehr and Weise, 2007]. 70% of non-acrocentric sSMC do not have phenotypic consequences, while the remaining 30% show different clinical manifestations [Liehr et al, 2006].…”

Characterization of the of the Pathological and Biochemical Markers That Correlate to the Clinical Features of Autism. Subproject 2. Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

“…Between 1994 and 2008, approximately 160 patients diagnosed with inverted (inv) dup (15) were characterized (Battaglia, 2008;Dennis et al, 2006;Webb, 1994;Webb et al, 1998;Wolpert et al, 2000a, b), and had a similar male:female ratio (3:1) to that reported in idiopathic autism (Bryson, 1996) and in probands with dup (15q) (Wolpert et al, 2000a).…”