Bilateral Helicoid Peri-papillary Sub-retinal Fibrosis Due to a Biallelic NR2E3 Mutation: Describing Variable Expressivity of a Single Genetic Mutation

Background: To describe different clinical presentations of NR2E3 (nuclear receptor subfamily 2, group E, member 3; OMIM 604485) recessive mutation in two families and within one family. Design: Interventional family study. Results: Our first case was a one-year-old male child with high hyperopia and refractive accommodative esotropia. In retinal examination, peri-papillary sub-retinal fibrosis with a helicoid configuration was observed in both eyes. Parents and the only sibling had no pathologic finding in the eyes. The child showed to have severely reduced responses in both photopic and scotopic electroretinogram components. In genetic investigation, a homozygous autosomal recessive mutation in NR2E3 gene was discovered in the affected child, while the other family members were heterozygous for this mutation. We followed up the patient for 3 years and no new lesion developed during this time period. The second case was a 13-year-old male child who was referred to retina clinic for decreased vision in the right eye. In retina examination, there were nummular pigmentary changes at the level of retinal pigment epithelium and along the vascular arcades with foveo-schitic changes in both eyes. A choroidal neovascularization (CNV) was noticed in macula of his right eye. Genetic evaluation proved the same mutation in NR2E3 gene. Family history was remarkable for an uncle, an aunt and two cousins with night blindness. In retina examination, asymptomatic father of proband showed to have slight pallor of optic nerve head and arterial narrowing in both eyes. Conclusion: NR2E3 gene mutation can cause heterogeneous clinical manifestations such as slight retinal changes in the absence of any visual symptoms to high hyperopia associated with helicoid peri-papillary sub-retinal fibrosis.

NEUROD1 Mutation in an Italian Patient With Maturity Onset Diabetes of the Young 6: a Case Report

Background and Aims: maturity onset diabetes of the young (MODY) is a monogenic, autosomal, dominant disease characterized by a single genetic mutation that results in beta-cells disfunction with consequent hyperglycemia. It represents a rare form of diabetes (1-2% of all the cases). Sulphonylureas (SU) represent the first line treatment for this form of diabetic disease. NEUROD1 is a transcription factor expressed by pancreatic and nervous tissues that is necessary for a proper development of beta cells. A mutation of NEUROD1 gene has been found to cause beta-cells dysfunction, inadequate insulin secretion, and hyperglycemia (MODY 6). A recent case report has documented for the first time a new missense mutation (p.Met114Leu c.340A> C), of the NEUROD1 gene pathogenetic for diabetes mellitus.Methods and Results: We report the case of a 50 years-old man who presented the same mutation, and who was able to suspend rapid insulin after the diagnosis and treatment with SU. Interestingly, our patient had an early onset dilated cardiomyopathy but no other data about cardiac diseases in patients with MODY 6 are available.Conclusions: Diagnostic criteria for MODY can overlap with other kinds of diabetes and most cases are still misdiagnosed as diabetes type 1 or 2. The disease should be suspected in patients with a strong family history of diabetes, normal BMI, early onset and no autoimmunity.

Uphill Task: Can We Ever Conquer Against New Emerging Viruses?

Every time there is a major infectious disease outbreak that scares us, such as Ebola in West Africa, Middle East Respiratory Syndrome (MERS) on the Arabian Peninsula and South Africa, and Zika virus in South and Central America and the Caribbean; this time arising from a mosquito-borne agent that has spread stealth around the globe [ 1]. It remains one of the great mysteries of the Zika epidemic: Why did a virus that existed for decades elsewhere in the world suddenly seem to become more destructive when it landed in Latin America? An intriguing study in mice, which has prompted some skepticism among experts, suggests that a single genetic mutation- called S139N, first arose in an Asian strain of the Zika virus in 2013, just before a small outbreak in French Polynesia, helped transform the Zika virus into a devastating force in Latin America [2 ]. JMS 2017;20(2):115-116

Generalized anxiety disorder and major depressive disorder comorbidity: an example of genetic pleiotropy?

Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are the most common type of anxiety-mood comorbidity. Up to 80% of subjects with lifetime GAD also have a comorbid mood disorder during their lifetime. Many hypotheses have been raised to explain such high comorbidity. Pleiotropy, i.e. a single genetic mutation explains (apparently) different disorders, is one of them and is hereby reviewed. Importance and reliability of GAD and MDD comorbidity (1); Evidence in favour of co-aggregation of GAD and MDD within families (the risk of one disorder in a proband increasing the risk for the other in relatives) (2); substantial heredity for both disorders according to twin studies with evidence for genetic correlation of unity between the two disorders (3); existence of numerous mechanisms (4) potentially linking the two disorders to common vulnerability genes, are all in accordance with such a hypothesis. Some examples of potentially shared mechanisms (such as CRF dysregulation or abnormal transcription factors) and possible common vulnerability genes (for example, the serotonin transporter gene) are given to highlight the pleiotropy hypothesis.