RESUMEN

The aim of this review is to describe a series of ten genetic diseases with Mendelian inheritance pattern in people of low- or middle-income countries, which can be easily identified with simple and affordable methods. Recent information shows that although genetic diseases account for more than 10% of infant mortality in such countries, testing, counseling, and treatment of genetic diseases is not a priority. The selection criteria for the genetic tests that are discussed in this review are: i) the frequency of the genetic disease in the general population, ii) the cost and ease of execution, and iii) the report of validated methods in the literature for the diagnosis of these diseases. The goal is to promote diagnosis of genetic diseases at low-cost and with relative ease, thereby enabling appropriate treatments, reducing mortality, and preventing genetic diseases in high-risk families.

Asunto(s)

Enfermedades Genéticas Congénitas/epidemiología , Enfermedades Genéticas Congénitas/genética , Pruebas Genéticas , Países en Desarrollo , Enfermedades Genéticas Congénitas/diagnóstico , Pruebas Genéticas/economía , Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Humanos , Tamizaje Masivo , Vigilancia de la Población , Factores Socioeconómicos

RESUMEN

Obesity is a major public health concern; despite evidence of high heritability, the genetic causes of obesity remain unclear. In this study, we assessed the presence of mutations in three genes involved in the hypothalamic leptin-melanocortin regulation pathway (leptin, LEP; leptin receptor, LEPR; and melanocortin-4 receptor, MC4R), which is important for energy homeostasis in the body, in a group of patients with severe obesity. For this study, we selected 77 patients who had undergone bariatric surgery and had a pre-operative body mass index (BMI) >35 kg/m2, early onset and a family history of being overweight. Candidate genes were screened by direct sequence analysis to search for rare genetic variations. The common LEP -2548 G/A polymorphism was also evaluated for its influence on the BMI (in obesity patients) and for obesity risk, using a case-control study involving 117 healthy individuals. Two different non-synonymous alterations in MC4R were found in two patients: the p.(Thr112Met), previously described in the literature as a probable gene involved in the obesity phenotype, and the novel p.(Tyr302Asp) variant, predicted to be pathogenic by in silico evaluations and family segregation studies. The LEP -2548 G/A polymorphism was not associated with the BMI or obesity risk. In conclusion, we have reported a novel mutation in MC4R in a family of Italian patients with severe obesity. Screening for MC4R could be important for directing the carriers of mutations towards therapy including partial agonists of the MC4R that could normalize their appetite and inhibit compulsive eating. Next-generation sequencing could be used to clarify the genetic basis of obesity in the future.

Asunto(s)

Leptina/genética , Obesidad Mórbida/genética , Receptor de Melanocortina Tipo 4/genética , Receptores de Leptina/genética , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense , Obesidad Mórbida/epidemiología , Obesidad Mórbida/patología , Linaje , Polimorfismo de Nucleótido Simple , Prevalencia

RESUMEN

Chronic fatigue syndrome (CFS) is a disease that can seriously impair one's quality of life; patients complain of excessive fatigue and myalgia following physical exertion. This disease may be associated with abnormalities in genes affecting exercise tolerance and physical performance. Adenosine monophosphate deaminase (AMPD1), carnitine palmitoyltransferase II (CPT2), and the muscle isoform of glycogen phosphorylase (PYGM) genes provide instructions for producing enzymes that play major roles in energy production during work. The aim of this study was to look for evidence of genotype-associated excessive muscle fatigue. Three metabolic genes (AMPD1, CPT2, and PYGM) were therefore fully sequenced in 17 Italian patients with CFS. We examined polymorphisms known to alter the function of these metabolic genes, and compared their genotypic distributions in CFS patients and 50 healthy controls using chi-square tests and odds ratios. One-way analysis of variance with F-ratio was carried out to determine the associations between genotypes and disease severity using CF scores. No major genetic variations between patients and controls were found in the three genes studied, and we did not find any association between these genes and CFS. In conclusion, variations in AMPD1, CPT2, and PGYM genes are not associated with the onset, susceptibility, or severity of CFS.

Asunto(s)

AMP Desaminasa/genética , Carnitina O-Palmitoiltransferasa/genética , Síndrome de Fatiga Crónica/genética , Glucógeno Fosforilasa de Forma Muscular/genética , AMP Desaminasa/metabolismo , Adolescente , Adulto , Carnitina O-Palmitoiltransferasa/metabolismo , Estudios de Casos y Controles , Síndrome de Fatiga Crónica/enzimología , Femenino , Expresión Génica , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Glucógeno Fosforilasa de Forma Muscular/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Adulto Joven

RESUMEN

In this study, we assessed the prevalence of polymorphisms in genes involved in hyperhomocysteinemia or hemostasis to shed light on their role, if any, in retinal vein occlusion (RVO). We recruited 37 Italian patients (17 men and 20 women) with a diagnosis of central or branch RVO based on fundus examination and retinal fluorescein angiography, as well as 45 healthy controls. Risk factors and family history of RVO of all subjects were recorded. The distributions of polymorphisms in patients and controls were evaluated using the χ(2) test and OR. We confirmed an increased risk in subjects with dyslipidemia (high density lipoprotein <59 mg/dL: 17.8% of controls, 43.2% of patients, P = 0.0002; low density lipoprotein >130 mg/dL: 26.7% controls, 54.1% patients, P = 0.0002), arterial hypertension (60% controls, 75.7% patients, P = 0.023), and high body mass index (28.9% controls, 70.3% patients, P < 0.0001, and excluded involvement of the selected polymorphisms in RVO. Overall, the tested polymorphisms did not appear to be useful for assessing predisposition or for the diagnosis and prognosis of RVO.

Asunto(s)

Predisposición Genética a la Enfermedad , Polimorfismo Genético , Oclusión de la Vena Retiniana/epidemiología , Oclusión de la Vena Retiniana/genética , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Italia/epidemiología , Masculino , Oportunidad Relativa , Vigilancia de la Población

RESUMEN

Hepatitis B virus (HBV) is the infectious agent of both acute and chronic hepatitis. HBV exists in multiple genotypic variants that differ in their capacity to become persistent chronic infections and in their clinical manifestations, including hepatocellular carcinoma. The 8 genotypes (A-H) of HBV show a specific worldwide geographic distribution and are correlated with different disease course, severity, and response to therapy. We isolated DNA from 75 HBV-positive blood donors, chosen randomly from the database of the National Blood Bank in Tirana, to specifically analyze the UGT1A1 polymorphism to determine its correlations with bilirubin levels and liver function. The large number of subjects who were HBV-positive carriers of heterozygosis or homozygosis for the UGT1A1*28 (TA)7 polymorphism suggests that these individuals may be more susceptible to cancer and should follow a strict regime of prevention.

Asunto(s)

Carcinoma Hepatocelular/genética , Glucuronosiltransferasa/genética , Cirrosis Hepática/genética , Neoplasias Hepáticas/genética , Albania , Bancos de Sangre , Donantes de Sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/patología , ADN Viral/genética , Femenino , Genotipo , Hepatitis B/genética , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/patogenicidad , Humanos , Hígado/lesiones , Hígado/virología , Cirrosis Hepática/sangre , Cirrosis Hepática/virología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad

RESUMEN

Mutations in more than 60 different genes have been associated with non-syndromic and syndromic retinitis pigmentosa (RP), a heterogeneous group of inherited retinal dystrophies. To increase the understanding of the molecular epidemiology of the disease in Italy, we analyzed 56 patients with syndromic and non-syndromic forms of RP attending the Retinitis Pigmentosa Center of San Paolo Hospital (Milan, Italy). Patients underwent detailed clinical examination. Genomic DNA isolated from peripheral blood samples was screened for mutations in different genes according to RP form by direct sequencing analysis. The impact of novel missense mutations on protein functions was predicted by in silico analysis and protein sequence alignment. Cosegregation analysis was performed between available family members. Forty-one of the 56 probands analyzed had non-syndromic and 15 had syndromic RP forms. Putative disease-causing mutations were identified in 19 of 56 unrelated RP probands. Mutation screening identified a total of 22 different heterozygous variants. Notably, 12 of these putative pathogenic mutations have not been previously reported. New variants were found to be located on the USH2A, RPGR, EYS, and RHO genes. All 3 new variants detected in X-linked RP probands were confirmed in other affected family members. We found a positivity rate of 24.4% and 60% for probands with non-syndromic and syndromic RP, respectively. This is the first report of RPGR X-linked RP proband-ORF15 mutations in Italian patients with X-linked (XL)-RP. In addition, this is the first report of data regarding the association between EYS mutations and non-syndromic RP forms in the Italian population.

Asunto(s)

Predisposición Genética a la Enfermedad/genética , Mutación , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/patología , Adulto , Anciano , Secuencia de Aminoácidos , Secuencia de Bases , Análisis Mutacional de ADN , Proteínas de la Matriz Extracelular/genética , Proteínas del Ojo/genética , Salud de la Familia , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Rodopsina/genética , Homología de Secuencia de Aminoácido , Síndrome , Adulto Joven

RESUMEN

Stargardt disease was diagnosed in 12 patients from 12 families using complete ophthalmologic examination, fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography. DNA was extracted for polymerase chain reaction (PCR) and direct DNA sequencing (ABCA4 gene). Genetic counseling and eye examination were offered to 16 additional family members. Various patterns of presentation were observed in patients with clinical diagnoses of Stargardt disease. The genetic study identified 2 mutations in 75% of families (9/12); a second mutation could not be found in the remaining 25% of families (3/12). The most frequent mutation was G1961E, found in 17% of families (2/12). This finding is similar to that of a previous analysis report of an Italian patient series. Four new mutations were also identified: Tyr1858Asp, Leu1195fsX1196, p.Tyr850Cys, and p.Thr959Ala. Our results suggest that PCR and direct DNA sequencing are the most appropriate techniques for the analysis of the ABCA4 gene. However, this method requires supplementation with specific PCR analysis to diagnose large deletions. The study of the families identified healthy carriers and affected subjects in presymptomatic stages and was also useful for evaluating the risk of transmission to progeny. Combined ophthalmologic and genetic evaluation enabled better clinical management of these families.

Asunto(s)

Transportadoras de Casetes de Unión a ATP/genética , Degeneración Macular/genética , Adulto , Anciano , Análisis Mutacional de ADN , Femenino , Genes Recesivos , Estudios de Asociación Genética , Humanos , Italia , Masculino , Persona de Mediana Edad , Mutación Missense , Adulto Joven