The Role of Mitochondria in Optic Atrophy With Autosomal Inheritance

Optic atrophy (OA) with autosomal inheritance is a form of optic neuropathy characterized by the progressive and irreversible loss of vision. In some cases, this is accompanied by additional, typically neurological, extra-ocular symptoms. Underlying the loss of vision is the specific degeneration of the retinal ganglion cells (RGCs) which form the optic nerve. Whilst autosomal OA is genetically heterogenous, all currently identified causative genes appear to be associated with mitochondrial organization and function. However, it is unclear why RGCs are particularly vulnerable to mitochondrial aberration. Despite the relatively high prevalence of this disorder, there are currently no approved treatments. Combined with the lack of knowledge concerning the mechanisms through which aberrant mitochondrial function leads to RGC death, there remains a clear need for further research to identify the underlying mechanisms and develop treatments for this condition. This review summarizes the genes known to be causative of autosomal OA and the mitochondrial dysfunction caused by pathogenic mutations. Furthermore, we discuss the suitability of available in vivo models for autosomal OA with regards to both treatment development and furthering the understanding of autosomal OA pathology.

Molecular changes in the Glucokinase gene (GCK) associated with the diagnosis of Maturity Onset Diabetes of the Young (MODY) in pregnant women and newborns

Background: Diabetes Mellitus is the most common metabolic alteration in gestation. Monogenic diabetes or Maturity-Onset Diabetes of the Young (MODY) consists in a subtype caused by primary defect in insulin secretion determined by dominant autosomal inheritance. Objectives: To analyze molecular changes of the Glucokinase gene (GCK) in pregnant women with hyperglycemia during gestation and in their neonates. Case study and Methods: We collected 201 blood samples, 128 from pregnant patients diagnosed with hyperglycemia and 73 from umbilical cord blood from neonates of the respective patients. We performed DNA extraction and polymerase chain reaction (PCR) to identify molecular changes in the GCK gene. Results: In a total of 201 samples (128 from mothers and 73 from neonates), we found changes in 21 (10.6%), 12 maternal samples (6.0%) and 9 neonatal samples (4.5%). DNA sequencing identified two polymorphisms and one deleterious MODY GCK-diagnostic mutation. Conclusions: The prevalence of molecular changes of the Glucokinase gene (GCK) and the deleterious MODY GCK-diagnostic mutation were, respectively, 9.3% and 0.7% in women with hyperglycemia during gestation and 12.5% and 1.3% in their neonates. The deleterious MODY GCK mutation identified is associated reduction in GCK activity and hyperglycemia. In the others molecular changes identified despite not having clinical significance, it was not possible to exclude phenotypic change. Therefore, these changes may interfere with the management and clinical outcome of the patients.

Evidence in the human species of Mendelian genetics (Autosomal Inheritance)

A genética mendeliana é um conjunto de princípios relacionados à transmissão hereditária das características de um organismo a seus filhos, onde forma a base principal da genética clássica que se originou dos trabalhos de Gregor Mendel publicados em 1865 e 1866. O presente trabalho teve como objetivo conhecer os traços morfológicos nos fenótipos da população humana na comunidade de Major Isidoro, AL. O trabalho foi aplicado no município de Major Isidoro, AL no povoado Cachoeira e teve como público alvo os moradores do mesmo. Foi realizada uma pesquisa utilizando um questionário contendo perguntas sobre as formas gênicas. Como observado o ser humano trás variação dos organismos uma herança autossômica semelhante entre seus pais. Isto é compreendido pela Genética, é notável a hereditariedade é a transmissão de características que os pais transmitem para os filhos.

Evidence in the human species of Mendelian genetics (Autosomal Inheritance)

A genética mendeliana é um conjunto de princípios relacionados à transmissão hereditária das características de um organismo a seus filhos, onde forma a base principal da genética clássica que se originou dos trabalhos de Gregor Mendel publicados em 1865 e 1866. O presente trabalho teve como objetivo conhecer os traços morfológicos nos fenótipos da população humana na comunidade de Major Isidoro, AL. O trabalho foi aplicado no município de Major Isidoro, AL no povoado Cachoeira e teve como público alvo os moradores do mesmo. Foi realizada uma pesquisa utilizando um questionário contendo perguntas sobre as formas gênicas. Como observado o ser humano trás variação dos organismos uma herança autossômica semelhante entre seus pais. Isto é compreendido pela Genética, é notável a hereditariedade é a transmissão de características que os pais transmitem para os filhos.

Severe Recurrent Epistaxis - The Main Symptom of Hereditary Haemorrhagic Teleangiectasia

Hereditary haemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is of dominant autosomal inheritance. Pathologic changes of vascular walls cause recurrent episodes of bleeding from many organ systems. Recurrent epistaxis is the first and the most frequent symptom of HHT. The causal therapy is not known but there are many therapeutic procedures improving the overall condition. We present a case of a 76-year-old man suffering from HHT, frequently hospitalized and treated for massive nose bleeding. In past a selective arterial embolization was performed thrice; nonetheless, the intensity and frequency of epistaxis remained unchanged. Anterior nasal package and electrocoagulation were performed repeatedly as the “first aid” treatment. In the article we also mention other therapeutic modalities for this diagnosis; unfortunately, their efficacy remains inadequate.

Ascending Aortic Aneurysm in a Case of Arterial Tortuosity Syndrome: A Rare Tortuous Disorder

Aortic aneurysms are a common entity among adults but very rare in the pediatric age-group. Association with autosomal inheritance is well established. We describe the unusual clinical presentation of a large ascending aortic aneurysm in a young child who was ultimately found to have severe diffuse arterial tortuosity.

When sleep-related hypermotor epilepsy (SHE) met Charles Darwin and Francis Galton

Sleep-related hypermotor epilepsy (SHE) is characterized by short-lasting seizures patterned by repetitive and stereotyped motor events in the same person. In autosomal dominant SHE, genetic factors play a well-known key role. In The Expression of Emotions in Man and Animals, Charles Darwin quotes a plausible example of SHE illustrated by his cousin Sir Francis Galton: “the gentleman…lay fast asleep on his back in bed, raising his right arm slowly in front of his face, up to his forehead, and then dropping it with a jerk, so that the wrist fell heavily on the bridge of his nose. The trick did not occur every night, but occasionally, and was independent of any ascertained cause. Sometimes it was repeated incessantly for an hour or more.” Similar manifestations during sleep occurred also in the patient's son and granddaughter, suggesting an autosomal inheritance without sex relationship. Differential diagnosis with REM behavior disorder and other parasomnias is discussed. To our knowledge, this could be the first description of a stereotyped SHE pattern with genetic transmission.