Paternally derived de novo interstitial duplication of proximal 15q in a patient with developmental delay

Mohandas, T.K.; Park, Jonathan P.; Spellman, Richard A.; Filiano, James J.; Mamourian, Alexander C.; Hawk, Arnold B.; Belloni, Dorothy R.; Noll, Walter W.; Moeschler, John B.

doi:10.1002/(sici)1096-8628(19990212)82:4<294::aid-ajmg4>3.3.co;2-l

Cited by 24 publications

(41 citation statements)

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“…Although less common, direct duplications of proximal 15q11-15q13 have been observed (Pettigrew et al 1987;Clayton-Smith et al 1993a;Browne et al 1997;Cook et al 1997Cook et al , 1998Mohandas et al 1999), some with the same breakpoints as PWS/AS deletions, whereas others have a more distal breakpoint similar to the large inv dup(15) (Repetto et al 1998;Robinson et al 1998). Patients with maternal duplications that include at least the PWS/AS critical region show devel-opmental delay, or autism (Browne et al 1997;Cook et al 1997Cook et al , 1998Repetto et al 1998), whereas a few individuals with paternal duplications have a nonspecific developmental delay (Mohandas et al 1999).…”

Section: Other 15q11-15q13 Rearrangementsmentioning

confidence: 99%

“…Patients with maternal duplications that include at least the PWS/AS critical region show devel-opmental delay, or autism (Browne et al 1997;Cook et al 1997Cook et al , 1998Repetto et al 1998), whereas a few individuals with paternal duplications have a nonspecific developmental delay (Mohandas et al 1999). Finally, a few triplication cases have been reported (Schinzel et al 1994;Cassidy et al 1996;Long et al 1998;Robinson et al 1998), as well as paracentric inversions of 15q11-15q13 (Clayton-Smith et al 1993b).…”

Section: Other 15q11-15q13 Rearrangementsmentioning

confidence: 99%

See 1 more Smart Citation

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

Ji¹,

Eichler²,

Schwartz³

et al. 2000

Genome Res.

231

158

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Chromosome-specific low-copy repeats, or duplicons, occur in multiple regions of the human genome. Homologous recombination between different duplicon copies leads to chromosomal rearrangements, such as deletions, duplications, inversions, and inverted duplications, depending on the orientation of the recombining duplicons. When such rearrangements cause dosage imbalance of a developmentally important gene(s), genetic diseases now termed genomic disorders result, at a frequency of 0.7–1/1000 births. Duplicons can have simple or very complex structures, with variation in copy number from 2 to >10 repeats, and each varying in size from a few kilobases in length to hundreds of kilobases. Analysis of the different duplicons involved in human genomic disorders identifies features that may predispose to recombination, including large size and high sequence identity between the recombining copies, putative recombination promoting features, and the presence of multiple genes/pseudogenes that may include genes expressed in germ cells. Most of the chromosome rearrangements involve duplicons near pericentromeric regions, which may relate to the propensity of such regions to accumulate duplicons. Detailed analyses of the structure, polymorphic variation, and mechanisms of recombination in genomic disorders, as well as the evolutionary origin of various duplicons will further our understanding of the structure, function, and fluidity of the human genome.

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Section: Other 15q11-15q13 Rearrangementsmentioning

confidence: 99%

Section: Other 15q11-15q13 Rearrangementsmentioning

confidence: 99%

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

Ji¹,

Eichler²,

Schwartz³

et al. 2000

Genome Res.

231

158

View full text Add to dashboard Cite

show abstract

“…Inherited int dup15 is rare, with only one published case involving the inheritance of a maternal duplication from the mother (Boyar et al, 2001), although some families with paternal duplication inherited from the father have been documented (Browne et al, 1997; Cook et al, 1997; Boyar et al, 2001; Veltman et al, 2005; Urraca et al, 2013; Al Ageeli et al, 2014). However, few cases of paternal duplication with developmental delay have been reported (Mohandas et al, 1999; Mao et al, 2000; Veltman et al, 2005). …”

Section: Introductionmentioning

confidence: 99%

A Rare Inherited 15q11.2-q13.1 Interstitial Duplication with Maternal Somatic Mosaicism, Renal Carcinoma, and Autism

et al. 2016

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Chromosome 15q11-q13.1 duplication is a common copy number variant associated with autism spectrum disorder (ASD). Most cases are de novo, maternal in origin and fully penetrant for ASD. Here, we describe a unique family with an interstitial 15q11.2-q13.1 maternal duplication and the presence of somatic mosaicism in the mother. She is typically functioning, but formal autism testing showed mild ASD. She had several congenital anomalies, and she is the first 15q Duplication case reported in the literature to develop unilateral renal carcinoma. Her two affected children share some of these clinical characteristics, and have severe ASD. Several tissues in the mother, including blood, skin, a kidney tumor, and normal kidney margin tissues were studied for the presence of the 15q11-q13.1 duplication. We show the mother has somatic mosaicism for the duplication in several tissues to varying degrees. A growth competition assay in two types of stem cells from duplication 15q individuals was also performed. Our results suggest that the presence of this interstitial duplication 15q chromosome may confer a previously unknown growth advantage in this particular individual, but not in the general interstitial duplication 15q population.

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“…Both paternal and maternal copies of this region are required for normal development, with loss of the paternal contribution leading to PWS and loss of the maternal contribution resulting in the AS phenotypes 13 . Surprisingly, Mohandas et al 18 reported a paternally derived de novo interstitial duplication of the proximal 15q containing the PWS/AS critical region in a patient with developmental delay, which raises the question as to whether or not all paternal duplications are benign with respect to phenotype. Mohandas et al 18 hypothesized that the breakpoints generating the 15q duplications, although clustered in the proximal 15q, may vary at the molecular level resulting in dosage changes for a different set of genes.…”

Section: Discussionmentioning

confidence: 99%

Tetrasomy 15q11-q13 identified by fluorescence in situ hybridization in a patient with autistic disorder

Silva

Vayego-Lourenço

Fett‐Conte

et al. 2002

Arq. Neuro-Psiquiatr.

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-We report a female child with tetrasomy of the 15q11-q13 chromosomal region, and autistic disorder associated with mental retardation, developmental problems and behavioral disorders. Combining classical and molecular cytogenetic approaches by fluorescence in situ hybridization technique, the karyotype was demonstrated as 47,XX,+mar.ish der(15)(D15Z1++,D15S11++,GABRB3++,PML-). Duplication of the 15q proximal segment represents the most consistent chromosomal abnormality reported in association with autism. The contribution of the GABA receptor subunit genes, and other genes mapped to this region, to the clinical symptoms of the disease is discussed.KEY WORDS: tetrasomy 15, 15q11-q13, autism, fluorescence in situ hybridization, GABA receptors.Identificação de tetrassomia 15q11-q13 por hibridação in situ fluorescente em uma paciente com distúrbio autístico RESUMO -Relatamos uma criança do sexo feminino com tetrassomia da região cromossômica 15q11-q13 e distúrbio autístico associado com retardo mental, problemas de desenvolvimento e distúrbios comportamentais. A combinação de metodologias da citogenética clássica e molecular pela técnica de hibridação in situ fluorescente, demonstrou o cariótipo como 47,XX,+mar.ish der(15) (D15Z1++,D15S11++,GABRB3++,PML). Duplicação do segmento 15q proximal representa a mais consistente anomalia cromossômica relatada em associação com autismo. A contribuição dos genes das subunidades do recepetor GABA, assim como outros genes mapeados nessa região, para os sintomas clínicos da doença é discutida. PALAVRAS-CHAVE: tetrassomia 15, 15q11-q13, autismo, hibridação in situ fluorescente, receptores GABA.

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Paternally derived de novo interstitial duplication of proximal 15q in a patient with developmental delay

Cited by 24 publications

References 0 publications

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

A Rare Inherited 15q11.2-q13.1 Interstitial Duplication with Maternal Somatic Mosaicism, Renal Carcinoma, and Autism

Tetrasomy 15q11-q13 identified by fluorescence in situ hybridization in a patient with autistic disorder

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