Clinical utility gene card for: Transient Neonatal Diabetes Mellitus, 6q24-related

Mackay, Deborah J G; Bens, Susanne; Nanclares, Guiomar Perez de; Siebert, Reiner; Temple, I. Karen

doi:10.1038/ejhg.2014.27

Cited by 19 publications

(18 citation statements)

References 16 publications

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“…There are several paternally imprinted regions that have been associated with disease to date [Liehr, 2010]. Paternal UPD 6q24 is associated with transient neonatal diabetes [Mackay et al, 2014]. Paternal UPD 11p15 is associated with Beckwith-Wiedemann syndrome [Weksberg et al, 2005].…”

Section: Discussionmentioning

confidence: 99%

Mosaic paternal genome‐wide uniparental isodisomy with down syndrome

Darcy

Atwal

Angell

et al. 2015

American J of Med Genetics Pt A

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We report on a 6-month-old girl with two apparent cell lines; one with trisomy 21, and the other with paternal genome-wide uniparental isodisomy (GWUPiD), identified using single nucleotide polymorphism (SNP) based microarray and microsatellite analysis of polymorphic loci. The patient has Beckwith-Wiedemann syndrome (BWS) due to paternal uniparental disomy (UPD) at chromosome location 11p15 (UPD 11p15), which was confirmed through methylation analysis. Hyperinsulinemic hypoglycemia is present, which is associated with paternal UPD 11p15.5; and she likely has medullary nephrocalcinosis, which is associated with paternal UPD 20, although this was not biochemically confirmed. Angelman syndrome (AS) analysis was negative but this testing is not completely informative; she has no specific features of AS. Clinical features of this patient include: dysmorphic features consistent with trisomy 21, tetralogy of Fallot, hemihypertrophy, swirled skin hyperpigmentation, hepatoblastoma, and Wilms tumor. Her karyotype is 47,XX,+21[19]/46,XX[4], and microarray results suggest that the cell line with trisomy 21 is biparentally inherited and represents 40-50% of the genomic material in the tested specimen. The difference in the level of cytogenetically detected mosaicism versus the level of mosaicism observed via microarray analysis is likely caused by differences in the test methodologies. While a handful of cases of mosaic paternal GWUPiD have been reported, this patient is the only reported case that also involves trisomy 21. Other GWUPiD patients have presented with features associated with multiple imprinted regions, as does our patient.

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Section: Discussionmentioning

confidence: 99%

Mosaic paternal genome‐wide uniparental isodisomy with down syndrome

Darcy

Atwal

Angell

et al. 2015

American J of Med Genetics Pt A

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“…In the fetal pancreas, both of these genes are expressed only from the paternal allele, and the imprinting is supported by a 1-kb differentially methylated region (DMR) that overlaps with the shared promoter of these genes [3]. 6q24-related transient neonatal diabetes is believed to be caused by an overexpression of PLAGL1 via one of three mechanisms: (1) paternal uniparental disomy of chromosome 6 (pUPD, 41%), (2) duplication of the paternal allele (33%), or (3) epimutation causing hypomethylation of the maternal allele (26%) [3,4]. [3,4].…”

Section: Introductionmentioning

confidence: 99%

Abnormalities in chromosome 6q24 as a cause of early‐onset, non‐obese, non‐autoimmune diabetes mellitus without history of neonatal diabetes

et al. 2015

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“…Transient neonatal diabetes mellitus type type 1 (TNDM1) is characterised by intrauterine growth retardation (IUGR) and hyperglycaemia in infancy. The diabetes mellitus typically develops in the first weeks of life and resolves by the age of 18 months; however, it is growing clear that individuals with TNDM are at risk of relapse, in adolescence or early adulthood, with type 2 diabetes [ 16 , 17 ]. Aside from these features, TNDM1 has no major cardinal features; however, individuals may have congenital abnormalities [ 18 ].…”

Section: Clinical and Molecular Findings In Imprinting Disordersmentioning

confidence: 99%

Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci

et al. 2015

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Congenital imprinting disorders (IDs) are characterised by molecular changes affecting imprinted chromosomal regions and genes, i.e. genes that are expressed in a parent-of-origin specific manner. Recent years have seen a great expansion in the range of alterations in regulation, dosage or DNA sequence shown to disturb imprinted gene expression, and the correspondingly broad range of resultant clinical syndromes. At the same time, however, it has become clear that this diversity of IDs has common underlying principles, not only in shared molecular mechanisms, but also in interrelated clinical impacts upon growth, development and metabolism. Thus, detailed and systematic analysis of IDs can not only identify unifying principles of molecular epigenetics in health and disease, but also support personalisation of diagnosis and management for individual patients and families.

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Clinical utility gene card for: Transient Neonatal Diabetes Mellitus, 6q24-related

Cited by 19 publications

References 16 publications

Mosaic paternal genome‐wide uniparental isodisomy with down syndrome

Mosaic paternal genome‐wide uniparental isodisomy with down syndrome

Abnormalities in chromosome 6q24 as a cause of early‐onset, non‐obese, non‐autoimmune diabetes mellitus without history of neonatal diabetes

Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci

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