Dataset Information

Segmental paternal uniparental disomy (patUPD) of 14q32 with abnormal methylation elicits the characteristic features of complete patUPD14.

ABSTRACT: Uniparental disomy (UPD) for chromosome 14 is associated with well-recognized phenotypes, depending on the parent of origin. Studies in mouse models and human patients have implicated the involvement of the distal region of the long arm of chromosome 14 in the distinctive phenotypes. This involvement is supported by the identification of an imprinting cluster at chromosome 14q32, encompassing the differentially methylated regions (DMRs), IG-DMR and MEG3-DMR, as well as the maternally expressed genes GTL2, DIO3, and RTL1 and the paternally expressed genes DLK1, RTL1as, and MEG8. Here we report on a preterm female infant with distal segmental paternal UPD14 (upd(14)pat) of 14q32-14q32.33, which resulted in thoracic deformity secondary to rib abnormalities ("coat-hanger" rib sign), polyhydramnios, and other congenital abnormalities characteristically described in cases of complete upd(14)pat. Microsatellite investigation demonstrated UPD of markers D14S250 and D14S1010, encompassing a approximately 3.5 Mb region of distal 14q and involving the imprinting cluster. This case provided insight into the etiology of the phenotypic effects of upd(14)pat, prompting methylation analysis of the GTL2 promoter and the DMR between GTL2 and DLK1. We compare the physical findings seen in this case with those of patients with other causes of abnormal methylation of 14q32, which consistently result in certain distinct clinical features, regardless of the cytogenetic and molecular etiology.

SUBMITTER: Irving MD

PROVIDER: S-EPMC3819653 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Segmental paternal uniparental disomy (patUPD) of 14q32 with abnormal methylation elicits the characteristic features of complete patUPD14.

Irving Melita D MD Buiting Karin K Kanber Deniz D Donaghue Celia C Schulz Reiner R Offiah Amaka A Mohammed Shehla N SN Oakey Rebecca J RJ

American journal of medical genetics. Part A 20100801 8

Uniparental disomy (UPD) for chromosome 14 is associated with well-recognized phenotypes, depending on the parent of origin. Studies in mouse models and human patients have implicated the involvement of the distal region of the long arm of chromosome 14 in the distinctive phenotypes. This involvement is supported by the identification of an imprinting cluster at chromosome 14q32, encompassing the differentially methylated regions (DMRs), IG-DMR and MEG3-DMR, as well as the maternally expressed g ...[more]

PMID: 20602488

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Project description:OBJECTIVE: To review all cases with segmental and/or complex uniparental disomy (UPD), to study aetiology and mechanisms of formation, and to draw conclusions. DESIGN: Searching published reports in Medline. RESULTS: The survey found at least nine cases with segmental UPD and a normal karyotype, 22 cases with UPD of a whole chromosome and a simple or a non-homologous Robertsonian translocation, eight cases with UPD and two isochromosomes, one of the short arm and one of the long arm of a non-acrocentric chromosome, 39 cases with UPD and an isochromosome of the long arm of two homologous acrocentric chromosomes, one case of UPD and an isochromosome 8 associated with a homozygous del(8)(p23.3pter), and 21 cases with UPD of a whole or parts of a chromosome associated with a complex karyotype. Segmental UPD is formed by somatic recombination (isodisomy) or by trisomy rescue. In the latter mechanism, a meiosis I error is associated with meiotic recombination and an additional somatic exchange between two non-uniparental chromatids. Subsequently, the chromatid that originated from the disomic gamete is lost (iso- and heterodisomy). In cases of UPD associated with one isochromosome of the short arm and one isochromosome of the long arm of a non-acrocentric chromosome and in cases of UPD associated with a true isochromosome of an acrocentric chromosome, mitotic complementation is assumed. This term describes the formation by misdivision at the centromere during an early mitosis of a monosomic zygote. In cases of UPD associated with an additional marker chromosome, either mitotic formation of the marker chromosome in a trisomic zygote or fertilisation of a gamete with a marker chromosome formed in meiosis by a disomic gamete or by a normal gamete and subsequent duplication are possible. CONCLUSIONS: Research in the field of segmental and/or complex UPD may help to explain undiagnosed non-Mendelian disorders, to recognise hotspots for meiotic and mitotic recombinations, and to show that chromosomal segregation is more complex than previously thought. It may also be helpful to map autosomal recessively inherited genes, genes/regions of genomic imprinting, and dysmorphic phenotypes. Last but not least it would improve genetic counselling.

Dataset Information

Segmental paternal uniparental disomy (patUPD) of 14q32 with abnormal methylation elicits the characteristic features of complete patUPD14.

Publications

Segmental paternal uniparental disomy (patUPD) of 14q32 with abnormal methylation elicits the characteristic features of complete patUPD14.

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