Genomic imprinting in diabetes

Abstract

Genomic imprinting refers to a class of transmissible genetic effects in which the expression of the phenotype in the offspring depends on the parental origin of the transmitted allele. The DNA from one parent may be epigenetically modified so that only a single allele of the imprinted gene is expressed in the offspring. Although imprinting has an important role in the regulation of growth and development through its role in regulating gene expression, its contribution to susceptibility to common complex disorders is not well understood. We summarize current views on the role of imprinting in diabetes and in particular chromosome 6q24-related transient neonatal diabetes mellitus, the best known example of an imprinted genetic disorder that leads to diabetes.

Pregnancy outcome of autosomal aneuploidies other than common trisomies detected by noninvasive prenatal testing in routine clinical practice

“…So far, there has been no definitive evidence of imprinting diseases related to the region of 7q11.23‐q21.11, 2p25.3‐p11.2, and 2q11.1‐q37.3 observed in 2 of our cases, and the pregnancy outcomes of both cases were normal. Imprinting diseases reported in the literature include transient neonatal diabetes mellitus related to 6q24, Russell‐Silver, Beckwith‐Wiedemann syndrome, Temple syndrome, UPD (14) pat syndrome, Angelman syndrome, Prader‐Willi Syndrome, UPD (20) mat syndrome, pseudohypoparathyoridism type Ib, and others. Thus, genetic counseling should take into account UPD when NIPT shows extra copies for chromosomes involved in well‐known imprinted disease loci, like pat6q24, mat7p11.2‐p12 and q32.2, segmental pat11p15.5, mat/pat14q32, mat/pat15q11‐q13, and UPD (20) mat (several loci involved)/pat20q13.3.…”

Clinical Update on Genetic and Autoimmune Biomarkers in Pediatric Diabetes

“…TNDM involves different single mutations of either the KCNJ11 or ABCC8 gene resulting in abnormalities in the potassium channels of β cells or imprinting errors in the PLAGL1 and HYMAI genes (Hattersley et al, 2009). Up to 70% of TNDM results from imprinted PLAGL1 and HYMAI genes in which only the paternal allele of the gene is expressed in offspring (Mitchell & Pollin, 2010). MODY subtypes are also caused by single gene mutations resulting in β-cell transcription factor errors and are classified according to the gene affected: MODY1 ( HNF4A gene), MODY 2 ( GCK gene), MODY 3 ( HNF1A gene), MODY 4 ( PDX1 gene), MODY 5 ( HNF1B gene), and MODY 6 ( NEUROD1 gene; Margulies et al, 2010; NCBI, 2011).…”

Транзиторный неонатальный сахарный диабет, ассоциированный с нарушением импринтинга хромосомы 6q24. Часть 2. Эпидемиология, этиология и патогенез

“…Примерно 40 % случаев 6q24-TNDM обусловлены отцовской однородительской дисомией, которая чаще представлена в виде изодисомии (две копии одной отцовской хромосомы) хромосомы 6. В 30 % случаев 6q24-TNDM у пациентов диагностируется дупликация (чаще субмикроскопическая) региона q24 копии отцовской хромосомы 6 [13,20].…”