Common deletion and duplication syndromes
Region: ISCA-37442-GainChromosome 6q24-related transient diabetes mellitus, neonatal
GRCh38 Position: 143922155-144095424
Haploinsufficiency Score:
Triplosensitivity Score: Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Required percent of overlap: 80%
Variant types: CNV Gain
1 review
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)
Transient neonatal diabetes mellitus-1 (TNDM1; '6q diabetes') is caused by overexpression of the paternal allele of the imprinted locus at chromosome 6q24, which contains PLAGL1.
Three genetic mechanisms had been shown to result in TNDM: paternal uniparental isodisomy of chromosome 6, paternally inherited duplication of 6q24, and a methylation defect at a CpG island overlapping exon 1 of ZAC/HYMAI (promoter of PLAGL1). Note that over 50% of individuals with TND and hypomethylation at 6q24 also show mosaic DNA hypomethylation at other imprinted loci throughout the genome and a range of additional clinical features.
Sources: Expert listCreated: 7 Dec 2020, 9:13 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Diabetes mellitus, transient neonatal 1, MIM# 601410
Publications
Details
- ISCA ID
- ISCA-37442-Gain
- ISCA Region Name
- Chromosome 6q24-related transient diabetes mellitus, neonatal
- Chromosome
- 6
- GRCh38 Coordinates
- 143922155-144095424
- Haploinsufficiency Score
- Triplosensitivity Score
- Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
- Required percent of overlap
- 80%
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
- Sources
-
- Expert Review Green
- Expert list
- Phenotypes
-
- Diabetes mellitus, transient neonatal 1, MIM# 601410
- Tags
- Clinvar variants
- Variants in
- Penetrance
- None
- Variant types
- CNV Gain
- Publications
History Filter Activity
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Region: isca-37442-gain has been classified as Green List (High Evidence).
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Region: isca-37442-gain has been classified as Green List (High Evidence).
Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Region: ISCA-37442-Gain was added Region: ISCA-37442-Gain was added to Common deletion and duplication syndromes. Sources: Expert list SV/CNV tags were added to Region: ISCA-37442-Gain. Mode of inheritance for Region: ISCA-37442-Gain was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for Region: ISCA-37442-Gain were set to 8842729 Phenotypes for Region: ISCA-37442-Gain were set to Diabetes mellitus, transient neonatal 1, MIM# 601410 Review for Region: ISCA-37442-Gain was set to GREEN