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Autistic disorder associated with a paternally derived unbalanced translocation leading to duplication of chromosome 15pter-q13.2: a case report.

Wu DJ, Wang NJ, Driscoll J, Dorrani N, Liu D, Sigman M, Schanen NC - Mol Cytogenet (2009)

Bottom Line: Autism spectrum disorders have been associated with maternally derived duplications that involve the imprinted region on the proximal long arm of chromosome 15.Using array comparative genome hybridization, we localized the breakpoints on both chromosomes and sequence homology suggests that the translocation arose from non-allelic homologous recombination involving the low copy repeats on chromosome 15.The child manifests many characteristics of the maternally-derived duplication chromosome 15 phenotype including developmental delays with cognitive impairment, autism, hypotonia and facial dysmorphisms with nominal overlap of the most general symptoms found in duplications of chromosome 9q34.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, University of Delaware, Newark, USA.

ABSTRACT
Autism spectrum disorders have been associated with maternally derived duplications that involve the imprinted region on the proximal long arm of chromosome 15. Here we describe a boy with a chromosome 15 duplication arising from a 3:1 segregation error of a paternally derived translocation between chromosome 15q13.2 and chromosome 9q34.12, which led to trisomy of chromosome 15pter-q13.2 and 9q34.12-qter. Using array comparative genome hybridization, we localized the breakpoints on both chromosomes and sequence homology suggests that the translocation arose from non-allelic homologous recombination involving the low copy repeats on chromosome 15. The child manifests many characteristics of the maternally-derived duplication chromosome 15 phenotype including developmental delays with cognitive impairment, autism, hypotonia and facial dysmorphisms with nominal overlap of the most general symptoms found in duplications of chromosome 9q34. This case suggests that biallelically expressed genes on proximal 15q contribute to the idic(15) autism phenotype.

No MeSH data available.


Related in: MedlinePlus

Quantitative Southern Blot analysis of the SNRPN exon α locus to determine gene dosage and methylation status. Southern blot analysis was performed using the SNRPN exon α probe, which detects a methylated maternal band at 4.2 kb and unmethylated paternal band at 0.8 kb. Densitometry was performed on the blot, which indicated that the proband (P) shows increased dosage of the paternal unmethylated allele when compared to the parental samples (F: Father, M: Mother) with a ratio of 1.47:1, consistent with paternal methylation of the der(15) chromosome. This was further supported by methylation specific PCR, which showed paternal:maternal ratio of 1.8:1 (not shown).
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Figure 1: Quantitative Southern Blot analysis of the SNRPN exon α locus to determine gene dosage and methylation status. Southern blot analysis was performed using the SNRPN exon α probe, which detects a methylated maternal band at 4.2 kb and unmethylated paternal band at 0.8 kb. Densitometry was performed on the blot, which indicated that the proband (P) shows increased dosage of the paternal unmethylated allele when compared to the parental samples (F: Father, M: Mother) with a ratio of 1.47:1, consistent with paternal methylation of the der(15) chromosome. This was further supported by methylation specific PCR, which showed paternal:maternal ratio of 1.8:1 (not shown).

Mentions: Genotyping was performed with a group of 29 short tandem repeat polymorphism (STRP) markers from chromosome 15, nine of which revealed evidence for an isodisomic paternal duplication of chromosome 15 based on increased peak heights for markers proximal to BP4 (Table 1). Similarly, genotyping was performed with 20 STRP markers from chromosome 9, which showed increased dosage at two of the most telomeric STRP markers based on peak heights (Table 2). Homozygosity for the parents and proband at STRP marker, D9S164, which is likely also included in the duplication may have precluded detection of a duplication at this locus because it was not possible to accurately compare peak height among the three individuals. Southern analysis of the SNRPN exon α locus showed a 1.47:1 dosage ratio of paternal to maternal alleles, consistent with paternal methylation of the derivative chromosome (Figure 1). Methylation specific PCR at this locus confirmed this result, with amplification of alleles at a ratio of 1.8:1 for unmethylated to methylated fragments (not shown).


Autistic disorder associated with a paternally derived unbalanced translocation leading to duplication of chromosome 15pter-q13.2: a case report.

Wu DJ, Wang NJ, Driscoll J, Dorrani N, Liu D, Sigman M, Schanen NC - Mol Cytogenet (2009)

Quantitative Southern Blot analysis of the SNRPN exon α locus to determine gene dosage and methylation status. Southern blot analysis was performed using the SNRPN exon α probe, which detects a methylated maternal band at 4.2 kb and unmethylated paternal band at 0.8 kb. Densitometry was performed on the blot, which indicated that the proband (P) shows increased dosage of the paternal unmethylated allele when compared to the parental samples (F: Father, M: Mother) with a ratio of 1.47:1, consistent with paternal methylation of the der(15) chromosome. This was further supported by methylation specific PCR, which showed paternal:maternal ratio of 1.8:1 (not shown).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803171&req=5

Figure 1: Quantitative Southern Blot analysis of the SNRPN exon α locus to determine gene dosage and methylation status. Southern blot analysis was performed using the SNRPN exon α probe, which detects a methylated maternal band at 4.2 kb and unmethylated paternal band at 0.8 kb. Densitometry was performed on the blot, which indicated that the proband (P) shows increased dosage of the paternal unmethylated allele when compared to the parental samples (F: Father, M: Mother) with a ratio of 1.47:1, consistent with paternal methylation of the der(15) chromosome. This was further supported by methylation specific PCR, which showed paternal:maternal ratio of 1.8:1 (not shown).
Mentions: Genotyping was performed with a group of 29 short tandem repeat polymorphism (STRP) markers from chromosome 15, nine of which revealed evidence for an isodisomic paternal duplication of chromosome 15 based on increased peak heights for markers proximal to BP4 (Table 1). Similarly, genotyping was performed with 20 STRP markers from chromosome 9, which showed increased dosage at two of the most telomeric STRP markers based on peak heights (Table 2). Homozygosity for the parents and proband at STRP marker, D9S164, which is likely also included in the duplication may have precluded detection of a duplication at this locus because it was not possible to accurately compare peak height among the three individuals. Southern analysis of the SNRPN exon α locus showed a 1.47:1 dosage ratio of paternal to maternal alleles, consistent with paternal methylation of the derivative chromosome (Figure 1). Methylation specific PCR at this locus confirmed this result, with amplification of alleles at a ratio of 1.8:1 for unmethylated to methylated fragments (not shown).

Bottom Line: Autism spectrum disorders have been associated with maternally derived duplications that involve the imprinted region on the proximal long arm of chromosome 15.Using array comparative genome hybridization, we localized the breakpoints on both chromosomes and sequence homology suggests that the translocation arose from non-allelic homologous recombination involving the low copy repeats on chromosome 15.The child manifests many characteristics of the maternally-derived duplication chromosome 15 phenotype including developmental delays with cognitive impairment, autism, hypotonia and facial dysmorphisms with nominal overlap of the most general symptoms found in duplications of chromosome 9q34.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, University of Delaware, Newark, USA.

ABSTRACT
Autism spectrum disorders have been associated with maternally derived duplications that involve the imprinted region on the proximal long arm of chromosome 15. Here we describe a boy with a chromosome 15 duplication arising from a 3:1 segregation error of a paternally derived translocation between chromosome 15q13.2 and chromosome 9q34.12, which led to trisomy of chromosome 15pter-q13.2 and 9q34.12-qter. Using array comparative genome hybridization, we localized the breakpoints on both chromosomes and sequence homology suggests that the translocation arose from non-allelic homologous recombination involving the low copy repeats on chromosome 15. The child manifests many characteristics of the maternally-derived duplication chromosome 15 phenotype including developmental delays with cognitive impairment, autism, hypotonia and facial dysmorphisms with nominal overlap of the most general symptoms found in duplications of chromosome 9q34. This case suggests that biallelically expressed genes on proximal 15q contribute to the idic(15) autism phenotype.

No MeSH data available.


Related in: MedlinePlus