Balkan Journal of Medical Genetics最新文献

The MEFV (familial Mediterranean fever gene) researches were performed in the population of the Republic of Azerbaijan in 2016-2021. Seven mutations of the MEFV gene were identified in heterozygous, homozygous and compound homozygous conditions: R761H, M694I, M694V, V726A, R202Q, M680I and E148Q. The E148Q and R202Q mutations were discovered in exon 2 and R761H M694I, M694V, V726A, M680I were found in exon 10 in the population of the Republic of Azerbaijan. The highest gene frequency of the MEFV gene examined in 42 patients was 42.85% in the M694V mutations. The second highest frequency was the R761H and the third most frequent mutation was V726A. According to world literature, five mutations, M694V, V726A, M694I, R202Q, M680I and E148Q, constitute 75.0% of all mutations found today. In our studies, these five mutations belong to the same group, and makes up 57.6% of the total mutations found. In order to prevent hereditary disease such as the familial Mediterranean fever (FMF) in the population of the Republic of Azerbaijan, it is planned to carry out prenatal diagnosis (PND) of the at-risk families.

Cystic fibrosis (CF) is an autosomal recessive disease. The genetic transition occurs with CF transmembrane conductance regulator (CFTR) gene mutation. We aimed to determine the frequency of CF mutations and also new mutations in the CFTR gene in neonates with respiratory distress. Newborn babies hospitalized due to respiratory distress were included in the patient group. The control group consisted of infants who had no respiratory distress. The CFTR genes of both groups were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. A total of 40 patients (20 in the patient group and 20 in the control group) were evaluated. The CFTR gene analysis was normal in 16 neonates in the patient group, whereas in others: A46D (c.137C>A) (n = 1), D1312G (c.3935A>G) (n = 1), R117H (c.350G>A) (n = 1), S1426P (c.4276T>C) (n = 1) heterozygotes were detected; CFTR gene analysis was normal at 14 neonates in the control group, whereas in others: E1228G (c.3683A>G) (n = 1), E217G (c.650A>G) (n = 1), E632TfsX9 (c1894_1895delAG) (n = 1), I807M (c.2421 A>G) (n = 2), S573F (c.1718C>T) (n = 1) heterozygotes were detected. There was no significant difference in the patient and control groups' CFTR gene analysis (p = 0.340). This study demonstrates the importance of CFTR gene analysis in asymptomatic newborn infants for follow-up and early diagnosis of CFTR-related disorders. In this study, a c.1894_1895delAG (E632TfsX9) heterozygous mutation detected in the CFTR gene in an asymptomatic newborn infant, was first encountered in the literature.

Introduction: Heterozygous pathogenic and likely pathogenic sequence variants in the RUNX1 (Runt-related Transcription Factor 1) gene are a common genetic cause of decreased platelet count and/or platelet dysfunction and an increased risk of developing myelodysplasia and acute myeloid leukemia. The majority of causative variants are substitutions, which rarely occur de novo. The aim of this case report is to present a patient with congenital thrombocytopenia caused by a deletion variant in exon 9 in the RUNX1 gene.

Case report: A one-month-old male infant was admitted to the Clinical Hospital Center Rijeka because of anemia and thrombocytopenia verified in the course of an acute viral infection. During follow-up, he occasionally had petechiae and ecchymoses on the lower extremities after mild trauma, with no other symptoms. The patient had persistent slightly decreased values of platelets with normal morphology, but with pathological aggregation with adrenaline and adenosine diphosphate. Due to the unclear etiology of persistent mild thrombocytopenia, he was referred for genetic testing at the age of five. Genomic DNA was isolated from the patient's peripheral blood and whole-exome sequencing was performed using the next-generation sequencing method. A heterozygous frameshift variant, c.1160delG (NM_001754.4), was identified in exon 9. The variant is classified as likely pathogenic.

Conclusion: To the best of our knowledge, the heterozygous variant c.1160delG in the RUNX1 gene was first described in our patient. Although pathogenic variants in the RUNX1 genes are very rare, persistently low platelet counts of unclear etiology should raise suspicion of an underlying genetic disorder.

Purpose: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal dysplastic syndrome presenting with keratitis, ichthyosis and sensorineural hearing loss. The most common causes of KID syndrome are heterozygous missense mutations in the GJB2 gene that codes for connexin 26.

Case report: During the ophthalmological examination, two adult females complained of recent worsening of visual acuity in both eyes. Anamnesis revealed that their eyes were red and irritated from early childhood onwards. Both of them had thickening and keratinisation of eyelid margins, lash loss, diffuse opacification of cornea and conjunctiva caused by keratinisation of eye surface, superficial and deep corneal vascularisation and corneal oedema. Partial sensorineural hearing loss and difficulties in speech were also noted along with typical ichthyosiform erythroderma. Genetic testing of the GJB2 gene revealed a heterozygous p.D50N mutation in both patients.Patients were treated with a combined topical corticosteroid and artificial tears therapy, with steroid therapy being intensified during the last month. The therapy increased the visual acuity by decreasing corneal oedema and by forming a more regular air-tear interface during the six months follow up. Subsequently, the disease progressed despite the continuation of the therapy.

Conclusion: This is the first report of Serbian patients with KID syndrome. Despite the administration of the combined topical corticosteroid and artificial tears therapy the disease is relentlessly progressive and therapeutic success of ophthalmological signs with local therapeutic modalities used so far had been disappointing.

Cardiomyopathies are a heterogeneous group of diseases predominantly affecting the heart muscle and often lead to progressive heart failure-related disability or cardiovascular death. Hypertrophic cardiomyopathy (HCM) is a cardiac muscle disorder mostly caused by the mutations in genes encoding cardiac sarcomere. Germ-line mutations in MYBPC3 causes hypertrophic cardiomyopathy (HCM). However, most of the HCM associated MYBPC3 mutations were truncating mutations. Extreme phenotypic heterogeneity was observed among HCM patients with MYBPC3 mutations. In this study, we investigated a Chinese man who presented with HCM. Whole exome sequencing identified a novel heterozygous deletion (c.3781_3785delGAGGC) in exon 33 of the MYBPC3 in the proband. This heterozygous variant causes frameshift (p.Glu1261Thrfs*3), which predicted to form a truncated MYBPC3 protein. The proband's father also carries this variant in a heterozygous state while the proband's mother did not harbor this variant. Here, we report on a novel deletion in the MYBPC3 gene associated with HCM. We also highlight the importance of whole exome sequencing for molecular diagnosis for the patients with familial HCM.

The purpose of the study is to determine the prevalence of interleukin (IL)-1A (rs1800587), IL-1B (rs1143634) and vitamin D receptor (VDR) (TaqI, rs731236) gene polymorphisms in the Turkish population and their association with Stage III Grade B/C periodontitis. Systemically and periodontally healthy individuals (N = 100) and Stage III Grade B/C periodontitis patients (N=100) based on clinical and radiographic examination were included in this research. Clinical attachment level, probing depth, bleeding on probing, plaque and gingival indices of the subjects were measured. Genotyping of IL-1A (rs1800587), IL-1B (rs1143634) and VDR (rs731236) polymorphisms was conducted by Real Time PCR. Allelic and genotypic distributions of IL-1A (rs1800587) gene polymorphism were not associated with periodontitis (p>0.05). In IL-1B (rs1143634) gene polymorphism, the C allele was detected more frequently in healthy individuals compared with the periodontitis patients (p=0.045). CC genotype and C allele in VDR (rs731236) gene polymorphism was higher in periodontitis patients (p=0.031, p=0.034, respectively). In comparison with Grade B periodontitis patients and healthy subjects, CC genotype and C allele were observed more frequently in the Grade B periodontitis in terms of alleles (C/T) and genotypes for VDR (rs731236) polymorphism (p=0.024, p=0.008, respectively). This study presents that the VDR (rs731236) polymorphism are associated with enhanced susceptibility to Stage III periodontitis in the Turkish population. Furthermore, VDR (rs731236) polymorphism may be used as an identification criteria to discriminate Grade B and Grade C in Stage III periodontitis.

Maturity-onset diabetes of the young (MODY) is the most common monogenic form of diabetes, accounting for 1-2% of all diabetes cases. At least 14 different MODY subtypes have been identified the most common of which is MODY 2 caused by mutations in the glucokinase (GSK) gene. The mild hyperglycemia of MODY 2 is often first detected during pregnancy. Patients with MODY are usually misdiagnosed as either idiopathic type 1 or type 2 diabetes. The recognition of MODY 2 during pregnancy has important clinical implications as the management of hyperglycemia may differ from the established algorithm in gestational diabetes. Fetus development could be seriously affected in case it has inherited the GSK mutation and maternal hyperglycemia is insulin treated to the pregnancy adopted glycemic targets. The case report describes the stepwise diagnostic approach to a 43-year-old woman with a history of gestational diabetes and persistent prediabetes who was found to be a carrier of a heterozygous pathogenic variant in GSK (c.184G>A) and discusses the possible genotype of her two children according to their birth weight.

Multiple sclerosis (MS) is an inflammatory disease characterized by demyelination and axonal degeneration affecting the central nervous system. Among the genetic factors suggested to be associated with this disease are polymorphisms to the vitamin D receptor (VDR) gene. We tested the hypothesis that polymorphisms in the vitamin D receptor (VDR) gene are associated with MS. The aim of the study was to investigate the relationship of MS with the VDR gene Fok-I, Bsm-I and Taq-I polymorphisms among the Turkish population. This study contains 271 MS patients and 203 healthy controls. Genomic DNA was isolated from the samples and the VDR gene Fok-I, Bsm-I and Taq-I polymorphism regions were amplified by polymerase chain reaction (PCR). The PCR products were digested, and the genotypes were determined based on size of digested PCR products. Our results demonstrate associations between MS and the distribution of the VDR gene Fok-I T/T polymorphism genotype in a dominant model, VDR gene Fok-I T allele frequency, distribution of VDR gene Taq-I C/C polymorphism genotype in a dominant model and VDR gene Taq-I C allele frequency (Pearson test, p<0.05). However, there was no association between MS and the VDR gene Bsm-I polymorphisms for the genotype distribution (Pearson test, p>0.05) or allele frequency (Pearson test, p>0.05). Fok-I and Taq-I VDR gene polymorphisms are significantly associated with MS in dominant, homozygote and heterozygote inheritance models among the Turkish population.

The increasing use of genomic testing in neonatal intensive care units (NICU) gives rise to ethical issues. Yet little is known regarding what health professionals implementing the testing think about its ethical aspects. We therefore explored the views of Australian clinical geneticists towards ethical issues in the use of genomic testing in the Neonatal Intensive care Unit (NICU). Semi-structured interviews with 11 clinical geneticists were conducted, transcribed and analysed thematically. Four themes were identified: 1) Consent: the craft is in the conversation, which encapsulated the challenges in the consent process, and with pre-test counseling; 2) Whose autonomy and who decides? This illustrates the balancing of clinical utility and potentially harms the test, and how stakeholder interests are balanced; 3) The winds of change and ethical disruption, recognizing that while professional expertise is vital to clinical decision-making and oversight of mainstreaming, participants also expressed concern over the size of the genetics workforce and 4). Finding Solutions - the resources and mechanisms to prevent and resolve ethical dilemmas when they arise, such as quality genetic counseling, working as a team and drawing on external ethics and legal expertise. The findings highlight the ethical complexities associated with genomic testing in the NICU. They suggest the need for a workforce that has the necessary support and skills to navigate the ethical terrain, drawing on relevant ethical concepts and guidelines to balance the interests of neonates, their careers and health professionals.

Syndromic craniosynostosis (SC) is a genetically determined premature closure of one or more of the cranial sutures, which may result in severe dysmorphism, increased intracranial pressure along with many other clinical manifestations. The considerable risk of complications along with their significant incidence makes these cranial deformations an important medical problem. Aiming to elucidate the complex genetic etiology of syndromic craniosynostosis, we investigated 39 children, screened systematically with a combination of conventional cytogenetic analysis, multiplex ligation-dependent probe amplification (MLPA) and array-based comparative genomic hybridisation (aCGH). Pathological findings were established in 15.3% (6/39) of the cases using aCGH, in 7.7% (3/39) using MLPA and 2.5% (1/39) using conventional karyotyping. About 12.8% (5/39) of the patients with normal karyotype carried submicroscopic chromosomal rearrangements. Duplications were found to be more common than deletions. Conclusion: The systematic genetic evaluation of children with SC revealed a high prevalence of submicrosopic chromosomal rearrangements (most commonly duplications). This suggests the leading role of those defects in the pathogenesis of syndromic craniosynostosis. The genetic complexity of SC was reaffirmed by the dis Bulgaria covery of pathological findings in various chromosomal regions. Certain genes were discussed in conjunction with craniosynostosis.