Genomic imprinting refers to the expression of parent-specific genes in diploid mammalian cells. MAGEL2 gene is a maternally imprinted gene that has been identified in mice and humans and is associated with the onset of puberty. The purpose of this study was to investigate its imprinting status and its relationship with the onset of puberty in Dolang sheep. The sequence of 3734 bp cDNA of MAGEL2 in Dolang sheep was obtained by cloning and sequencing, encoding 1173 amino acids. The results of the nucleotide and amino acid similarity analysis showed that it was highly conserved among different mammalian species. The MAGEL2 gene was expressed monoallelically in the tissues of adult and neonatal umbilical cords, and the expressed allele was paternally inherited. Real Time quantitative PCR (RT-qPCR) results showed that the MAGEL2 gene was highly expressed in the hypothalamus and pituitary gland, increased significantly from prepuberty to puberty, and decreased significantly after puberty. This study suggests that MAGEL2 is a paternally expressed and maternally imprinted gene in Dolang sheep, which may be involved in the initiation of puberty in Dolang sheep. This study provides a theoretical basis for further research on the mechanism of the imprinted gene MAGEL2 regulating the onset of puberty in sheep, and provides a new idea for the future research on the mechanism of onset of puberty in sheep.

Schaaf-Yang syndrome (SYS) is a rare neurodevelopmental disorder caused by pathogenic variants in the MAGEL2 gene. It is usually a postnatal diagnosis in infants with muscular hypotonia and feeding difficulties. There are no cases diagnosed antenatally. During pregnancy, the most common findings reported are polyhydramnios and decreased fetal movements, which are relatively common and unspecific.We present one case of fetal clubfoot and clinodactyly in a fetus postnatally diagnosed with SYS, as well as a brief review of the prenatal findings associated with this syndrome.

Genomic imprinting is the epigenetic mechanism of transcriptional regulation that involves differential DNA methylation modification. Comparative analysis of imprinted genes between species can help us to investigate the biological significance and regulatory mechanisms of genomic imprinting. MKRN3, MAGEL2 and NDN are three maternally imprinted genes identified in the human PWS/AS imprinted locus. This study aimed to assess the allelic expression of MKRN3, MAGEL2 and NDN and to examine the differentially methylated regions (DMRs) of bovine PWS/AS imprinted domains. An expressed single-nucleotide polymorphism (SNP)-based approach was used to investigate the allelic expression of MKRN3, MAGEL2 and NDN genes in bovine adult tissues and placenta. Consistent with the expression in humans and mice, we found that the MKRN3, MAGEL2 and NDN genes exhibit monoallelic expression in bovine somatic tissues and the paternal allele expressed in the bovine placenta. Three DMRs, PWS-IC, MKRN3 and NDN DMR, were identified in the bovine PWS/AS imprinted region by analysis of the DNA methylation status in bovine tissues using the bisulfite sequencing method and were located in the promoter and exon 1 of the SNRPN gene, NDN promoter and 5\' untranslated region (5\'UTR) of MKRN3 gene, respectively. The PWS-IC DMR is a primary DMR inherited from the male or female gamete, but NDN and MKRN3 DMR are secondary DMRs that occurred after fertilization by examining the methylation status in gametes.

Schaaf-Yang syndrome is a genetic disorder caused by mutations in the paternal allele of the MAGEL2 gene. Developmental delay, feeding difficulties, joint contractures and a high prevalence of autism spectrum disorders are characteristic of the syndrome. Endocrine abnormalities include mostly various pituitary hormonal deficiencies, presenting as hypoglycemia in 48% of reported cases. Persistent hyperinsulinism was only described in two siblings and responded to diazoxide treatment. We describe a unique case of an infant with Schaaf-Yang syndrome that presented with persistent hyperinsulinism unresponsive to diazoxide. Furthermore, we conducted a literature review of the endocrine abnormalities described in MAGEL2 related disorders. The case presented expands the clinical phenotype of Schaaf-Yang syndrome and emphasizes the importance of endocrine follow-up in these patients. Further investigation into the role of MAGEL2 in the regulation of pancreatic beta-cell insulin secretion, will improve our understanding of the abnormalities in glucose regulation in this syndrome.