Introduction: Wilson disease (WD) is an inherited disorder of copper metabolism presenting with a variety of symptoms but commonly as a liver or neuropsychiatric disease. Abnormal evoked responses are constantly found among patients with neurologic manifestations and sometimes in patients with hepatic presentation or in presymptomatic siblings. The aim of our study was to assess visual and brainstem auditory evoked potentials (BAEP) in patients with various presentation of WD.
View Article and Find Full Text PDFIdiopathic scoliosis (IS) is a common medical condition in children, characterized by three-dimensional spinal curve and strong evidence of genetic predisposition. The purpose of the present case-control study is to examine the association between the polymorphic variant rs11190870 (T/C), near the LBX1 gene, and IS predisposition in distinct subgroups based on age at onset, family history and gender. A total of 127 IS patients and 254 unrelated controls of Southeastern European descent were recruited.
View Article and Find Full Text PDFCongenital muscle dystrophies (CMD) are genetically and clinically heterogeneous hereditary myopathies mainly with autosomal recessive type of inheritance. The most common form worldwide is considered to be merosin-deficient muscle dystrophy type 1A, called MDC1A (due to laminin-2 defects as a result of gene mutation), accounting for 30-40% of total cases of CMD. The exact molecular and clinical diagnoses, respectively, are a prerequisite for the most effective treatment; sometimes orphan drugs exist for some rare diseases.
View Article and Find Full Text PDFIdiopathic scoliosis (IS) is a common medical condition beginning in childhood and characterized by strong evidence for a genetic susceptibility to three-dimensional spinal deformity. The primary goal of the current case-control study is to examine the association between the (-509C/T) functional polymorphic variant and genetic predisposition to IS in the Bulgarian population and the genotype-phenotype correlations in distinct case-control subgroups based on age at onset, family history, and gender. A total of 127 patients with primary scoliosis and 254 gender-matched control subjects were recruited.
View Article and Find Full Text PDFRenal cysts are common malformation during the prenatal and postnatal period and frequent cause of chronic kidney or ESRD. More than 70 genes have been shown to play role in their pathology. Part of them are responsible for the structure and function of the cilia, which assigns a large proportion of the renal cystic diseases in the ciliopathies.
View Article and Find Full Text PDFThe vast majority of patients with Nijmegen Breakage Syndrome (NBS) are of Slavic origin and carry a deleterious deletion (c.657del5; rs587776650) in the NBN gene on chromosome 8q21. This mutation is essentially confined to Slavic populations and may thus be considered a Slavic founder mutation.
View Article and Find Full Text PDFThe concept of disease-modifier genes as an element of genetic heterogeneity has been widely accepted and reported. The aim of the current study is to investigate the association between the promoter polymorphism TPH1 (rs10488682) and progression of idiopathic scoliosis (IS) in Eastern European population sample. A total of 105 patients and 210 healthy gender-matched controls were enrolled in this study.
View Article and Find Full Text PDFCharcot-Marie-Tooth disease encompasses a genetically heterogeneous class of heritable polyneuropathies that result in axonal degeneration in the peripheral nervous system. Charcot-Marie-Tooth type 2D neuropathy (CMT2D) is caused by dominant mutations in glycyl tRNA synthetase (GARS). Mutations in the mouse Gars gene result in a genetically and phenotypically valid animal model of CMT2D.
View Article and Find Full Text PDFBackground: The current consensus on idiopathic scoliosis maintains that it has a multifactorial etiology with genetic predisposing factors.
Aim: Estrogen receptor alpha gene has been considered as candidate gene of idiopathic scoliosis.
Material And Methods: We conducted a case-control study of Bulgarian population samples (eighty patients with idiopathic scoliosis and one hundred-sixty healthy unrelated gender-matched controls) trying to investigate the association between common genetic polymorphisms of estrogen receptor alpha and the susceptibility to idiopathic scoliosis.
Study Design: A case-control study was performed on 105 patients with idiopathic scoliosis (IS) and 210 unrelated gender-matched controls from Bulgarian population.
Objective: Investigation of the association between common genetic polymorphisms of IL-6 and MMP3 genes and the etiology and progression of IS among Bulgarian patients.
Summary Of Background Data: The IL-6 and MMP3 genes have been considered as candidate genes of IS in Caucasian population.
Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant congenital disorder (prevalence, 1:125000-720000) characterized by broad thumbs and halluces, facial dysmorphism, psychomotor development delay, skeletal defects, abnormalities in the posterior fossa, and short stature. The purpose of this study was to use targeted exome sequencing to identify the genetic cause of RSTS in a 6.5-year-old girl presenting typical features of this condition.
View Article and Find Full Text PDFThe mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects.
View Article and Find Full Text PDFIdiopathic scoliosis (IS) is a complex genetic disorder of the musculoskeletal system, characterized by three-dimensional rotation of the spine with unknown etiology. For the aims of the current study we selected 3 single nucleotide polymorphisms with a low incidence of the polymorphic allele in Bulgarian population, AMPD1 (rs17602729), VDR (rs2228670), and IGF-1 (rs5742612), trying to investigate the association between these genetic polymorphisms and susceptibility to and progression of IS. The polymorphic regions of the genes were amplified by polymerase chain reaction (PCR).
View Article and Find Full Text PDFIdiopathic scoliosis (IS) is the most common spinal disorder in children and adolescents. The current consensus on IS maintains that it has a multifactorial etiology with genetic predisposition factors. In the present study the association of two functional polymorphisms of leptin (rs7799039) and BMP4 (rs4898820) with susceptibility to IS and curve severity was investigated in a Bulgarian population sample.
View Article and Find Full Text PDFAnal Cell Pathol (Amst)
March 2016
Scoliotic human nuclei pulposi can respond to exogenous proinflammatory stimuli by secreting increased amounts of interleukin-6 (IL-6). The G/C polymorphism of the promoter region of IL-6 gene influences levels and functional activity of the IL-6 protein. We conducted a case-control study of eighty patients with idiopathic scoliosis (IS) and one hundred sixty healthy unrelated gender-matched controls trying to investigate the association between IS and the IL-6 promoter polymorphism at -174 position (rs1800795 G/C) in Bulgarian population.
View Article and Find Full Text PDFBackground: About 3885 women are diagnosed with breast cancer and 1285 die from the disease each year in Bulgaria. However no genetic testing to identify the mutations in high-risk families has been provided so far.
Methods: We evaluated 200 Bulgarian women with primary invasive breast cancer and with personal/ family history of breast cancer for the presence of unequivocally damaging germline mutations in BRCA1/2 using Sanger sequencing.
Investigation of 31 of Roma patients with congenital lactic acidosis (CLA) from Bulgaria identified homozygosity for the R446* mutation in the PDHX gene as the most common cause of the disorder in this ethnic group. It accounted for around 60% of patients in the study and over 25% of all CLA cases referred to the National Genetic Laboratory in Bulgaria. The detection of a homozygous patient from Hungary and carriers among population controls from Romania and Slovakia suggests a wide spread of the mutation in the European Roma population.
View Article and Find Full Text PDFHere we report recruitment of a three-generation Romani (Gypsy) family with autosomal dominant cone-rod dystrophy (adCORD). Involvement of known adCORD genes was excluded by microsatellite (STR) genotyping and linkage analysis. Subsequently, two independent total-genome scans using STR markers and single-nucleotide polymorphisms (SNPs) were performed.
View Article and Find Full Text PDFEXT1/EXT2-CDG (Multiple cartilagineous exostoses, hereditary multiple osteochondroma (MO); OMIM 133700/133701) are common defects of O-xylosylglycan glycosylation. The diagnostic criteria are at least two osteochondromas of the juxta-epiphyseal region of long bones with in the majority of cases a positive family history and/or mutation in one of the EXT genes. The authors report data on clinical symptoms and complications of 23 patients (from 16 families), discussing the family history, age of diagnosis, new clinical and molecular data.
View Article and Find Full Text PDFMutations in SCN1A gene, encoding the voltage-gated sodium channel α1-subunit, are found to be associated with severe myoclonic epilepsy in infancy or Dravet syndrome (DS), but only rarely with the myoclonic astatic epilepsy (MAE, or Doose syndrome). We report on two patients with SCN1A mutations and severe epilepsy within the spectrum of generalized epilepsy with febrile seizures plus syndrome (GEFS+), the phenotypes being consistent with DS and MAE, respectively. Analysis of SCN1A revealed a heterozygous de novo frameshift mutation (c.
View Article and Find Full Text PDFThe μ-opioid receptor is the primary site of action of most opioids. The 118A>G (rs1799971) polymorphism in exon 1 of the μ-opioid receptor gene (OPRM1) leads to an Asn40Asp amino acid change that affects a putative N-glycosylation site. It has been widely investigated for association with alcohol and drug dependence and pain sensitivity, with mixed results.
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