The KCNH1 gene encodes the Kv10.1 (Eag1) ion channel, a member of the EAG (ether-à-go-go) family of voltage-gated potassium channels. Recent studies have demonstrated that KCHN1 mutations are implicated in Temple-Baraitser and Zimmermann-Laband syndromes and other forms of developmental deficits that all present with mental retardation and epilepsy, suggesting that Kv10.1 might be important for cognitive development in humans. Although the Kv10.1 channel is mainly expressed in the mammalian brain, its ectopic expression occurs in 70% of human cancers. Cancer cells and tumors expressing Kv10.1 acquire selective advantages that favor cancer progression through molecular mechanisms that involve several cellular pathways, indicating that protein-protein interactions may be important for Kv10.1 influence in cell proliferation and tumorigenesis. Several studies on transcriptional and post-transcriptional regulation of Kv10.1 expression have shown interesting mechanistic insights about Kv10.1 role in oncogenesis, increasing the importance of identifying the cellular factors that regulate Kv10.1 expression in tumors.

While the majority of cases of primary aldosteronism (PA) are sporadic, four forms of autosomal-dominant inheritance have been described: familial hyperaldosteronism (FH) types I to IV. FH-I, also called glucocorticoid-remediable aldosteronism, is characterized by early and severe hypertension, usually before the age of 20 years. It is due to the formation of a chimeric gene between the adjacent CYP11B2 and CYP11B1 genes (coding for aldosterone synthase and 11β-hydroxylase, respectively). FH-I is often associated with family history of stroke before 40years of age. FH-II is clinically and biochemically indistinguishable from sporadic forms of PA and is only diagnosed on the basis of two or more affected family members. No causal genes have been identified so far and no genetic test is available. FH-III is characterized by severe and early-onset hypertension in children and young adults, resistant to treatment and associated with severe hypokalemia. Mild forms, resembling FH-II, have been described. FH-III is due to gain-of-function mutations in the KCNJ5 gene. Recently, a new autosomal-dominant form of familial PA, FH-IV, associated with mutations in the CACNA1H gene, was described in patients with hypertension and PA before the age of 10years. In rare cases, PA may be associated with complex neurologic disorder involving epileptic seizures and cerebral palsy (Primary Aldosteronism, Seizures, and Neurologic Abnormalities [PASNA]) due to de novo germline CACNA1D mutations.

Maturity-onset diabetes of the young (MODY) is a group of monogenic diseases that results in primary defects in insulin secretion and dominantly inherited forms of nonautoimmune diabetes. Although many genes may be associated with monogenic diabetes, heterozygous mutations in 6 of them are responsible for the majority of cases of MODY. Glucokinase (GCK)-MODY is due to mutations in the glucokinase gene, 3 MODY subtypes are associated with mutations in the hepatocyte nuclear factor (HNF) transcription factors, and 2 others with mutations in ABCC8 and KCNJ11, which encode the subunits of the ATP-dependent potassium channel in pancreatic beta cells. GCK-MODY and HNF1A-MODY are the most common subtypes. The clinical presentation of MODY subtypes has been reported to differ according to the gene involved, and the diagnosis of MODY may be considered in various clinical circumstances. However, except in patients with GCK-MODY whose phenotype is very homogeneous, in most cases the penetrance and expressivity of a given molecular abnormality vary greatly among patients and, conversely, alterations in various genes may lead to similar phenotypes. Moreover, differential diagnosis among more common forms of diabetes may be difficult, particularly with type 2 diabetes. Thus, careful assessment of the personal and family histories of patients with diabetes is mandatory to select those in whom genetic screening is worthwhile. The diagnosis of monogenic diabetes has many consequences in terms of prognosis, therapeutics and family screening.

Antibodies to different membrane proteins, namely acetylcholine receptor, muscle specific kinase and low density lipoprotein receptor-related protein 4, at the neuromuscular junction are well recognised in myasthenia gravis, although the mechanisms responsible for the muscle distribution and fluctuations in function are still not very clear, and some of the issues are discussed below. In addition, the involvement of antibodies to the potassium channel complex proteins in neuromyotonia, help to lead to a better understanding of immunotherapy-responsive central nervous system diseases.