We present a patient with neonatal MAS who initially presented with neonatal diabetes and concern for congenital cardiac disease, and subsequently was found to have significant ACTH-independent neonatal Cushing syndrome.
Applying a GRS 50th T1D centile cutoff in 48 NDM patients with no known genetic cause identified those most likely to have a novel monogenic etiology by highlighting patients with probable early-onset T1D (GRS >50th T1D centile) who were diagnosed later and had less syndromic presentation but additional autoimmune features compared with those with proven monogenic NDM.
In humans, a mutation in the Glis2 gene has been linked to the development of nephronophthisis (NPHP), a recessive cystic kidney disease, while mutations in Glis3 lead to an extended multisystem phenotype that includes the development of neonatal diabetes, polycystic kidneys, congenital hypothyroidism, and facial dysmorphism.
Emerging data demonstrate that mutations of Krüppel-like factor-11 (KLF11), a gene coding maturity-onset diabetes mellitus of the young type 7 (MODY7), contribute to the development of neonatal diabetes mellitus.
These observations demonstrate that mitotic recombination of chromosome 20 can also give rise to UPD and PHP, a situation similar to other imprinting disorders, such as Beckwith-Wiedemann syndrome or neonatal diabetes.
These observations demonstrate that mitotic recombination of chromosome 20 can also give rise to UPD and PHP, a situation similar to other imprinting disorders, such as Beckwith-Wiedemann syndrome or neonatal diabetes.
These observations demonstrate that mitotic recombination of chromosome 20 can also give rise to UPD and PHP, a situation similar to other imprinting disorders, such as Beckwith-Wiedemann syndrome or neonatal diabetes.
Heterozygosity for PDX-1 mutations was found in some individuals with a newly characterized subtype of maturity-onset diabetes of the young (MODY4) and in others with type 2 DM.
The homologous human gene ZAC (also known as LOT1 and PLAGLI) is a candidate gene for transient neonatal diabetes (TNDM), an imprinted disorder associated with paternal duplication for 6q24 and characterized by intrauterine growth retardation and insulin dependence.
The homologous human gene ZAC (also known as LOT1 and PLAGLI) is a candidate gene for transient neonatal diabetes (TNDM), an imprinted disorder associated with paternal duplication for 6q24 and characterized by intrauterine growth retardation and insulin dependence.
It therefore appears unlikely that PAX4 is involved in the aetiology of Wolcott-Rallison syndrome, though it remains a good candidate for other forms of neonatal diabetes mellitus.
This can be seen with dramatic impact on clinical care, in patients with genetic forms of diabetes such as Maturity Onset Diabetes of the Young caused by HNF1A mutations, and Neonatal diabetes due to activating mutations in ABCC8 or KCNJ11.
The most frequent genes involved in monogenic diabetes [KCNJ11 and INS for neonatal diabetes and HNF1A and HNF4A for maturity-onset diabetes of the young (MODY)] were directly sequenced.
Monogenic forms of diabetes like MODY and neonatal diabetes have paved the way for precision medicine in diabetes, as carriers of unique mutations require unique treatment.
Mutations in the genes encoding the pancreatic K<sub>ATP</sub> channels can also lead to different types of diabetes (including neonatal diabetes mellitus (NDM) and Maturity Onset Diabetes of the Young, MODY), and defects in the solute carrier family 2 member 2 (<i>SLC2A2</i>) leads to diabetes mellitus as part of the Fanconi-Bickel syndrome.
The precision medicine approach of tailoring treatment to the individual characteristics of each patient or subgroup has been a great success in monogenic diabetes subtypes, MODY and neonatal diabetes.
Heterozygous mutations in the insulin gene that affect proinsulin biosynthesis and folding are associated with a spectrum of diabetes phenotypes, from permanent neonatal diabetes to MODY.
The knowledge of typical clinical features such as mode of inheritance, age at diagnosis and impaired insulin secretion, as well as genetic testing establishes the diagnosis of MODY, mitochondrial diabetes and neonatal diabetes.
The most frequent genes involved in monogenic diabetes [KCNJ11 and INS for neonatal diabetes and HNF1A and HNF4A for maturity-onset diabetes of the young (MODY)] were directly sequenced.