Murat Erdogan

Prediction, prevention and personalisation of medication for the prenatal period: genetic prenatal tests for both rare and common diseases

Genetic testing usually helps physicians to determine possible genetic diseases in unborn babies, genetic disorders of patients and the carriers who might pass the mutant gene on to their children. They are performed on blood, tissues or other body fluids. In recent years, the screening tests and diagnostic tests have improved quickly and, as a result, the risks of pregnancy can be determined more commonly and physicians can diagnose several genetic disorders in the prenatal period. Detecting the abnormalities in utero enables correct management of the pregnancy, prenatal and postnatal medical care, and it is also important for making well informed decisions about continuing or terminating a pregnancy. Besides the improvements of conventional invasive diagnostic tests, the discovery of circulating cell-free foetal nucleic acids in maternal plasma has developed a new point of view for non-invasive prenatal diagnosis recently.

Increased vitamin D receptor gene expression and rs11568820 and rs4516035 promoter polymorphisms in autistic disorder

Although there are a large number of sequence variants of different genes and copy number variations at various loci identified in autistic disorder (AD) patients, the pathogenesis of AD has not been elucidated completely. Recently, in AD patients, a large number of expression array and transcriptome studies have shown an increase in the expression of genes especially related to innate immune response. Antimicrobial effects of vitamin D and VDR are exerted through Toll-Like-Receptors (TLR) which have an important role in the innate immune response, are expressed by antigen presenting cells and recognize foreign microorganisms. In this study, age and gender matched 30 patients diagnosed with AD and 30 healthy controls were included in the study. Comparatively whole blood VDR gene expression and rs11568820 and rs4516035 SNP profile of the promoter region of the VDR gene were investigated by real time PCR. Whole blood VDR gene expression was significantly higher in the AD group compared to control subjects (p < 0.0001). There were no significant differences among allele and genotype distribution of rs11568820 and rs4516035 polymorphisms between AD patients and controls. The increase of VDR gene expression in patients with AD may be in accordance with an increase in the innate immune response in patients with AD. Furthermore, this study will stimulate new studies in order to clarify the relationship among AD, vitamin D, VDR, and innate immunity.

Tc-99m MDP Bone SPECT/CT Findings of a Patient Detected with a New Mutation in LEMD3 Gene: A Case of Osteopoikilosis

Osteopoikilosis is an inherited condition with autosomal dominant trait resulting in sclerotic foci throughout the skeleton. It has been suggested that loss-of-function mutations of LEMD3 gene located on 12q14.3 result in osetopoikilosis. A bp heterozygote deletion was detected in our patient at the cytosine nucleotide at position 1105 with molecular genetic analysis. Although this mutation has not been previously described, it was considered to be the most likely cause of the disease in our patient due to frame shift and premature stop codon formation. As in our case, three phase bone scintigraphy and whole body imaging did not reflect the true extent of lesion sites and lesion activity. SPECT/CT images could reflect lesion location and activity more accurately, and could be a good alternative for differential diagnosis of unexplained bone pain and sclerotic lesions in one examination.

Decreased disulphide/thiol ratio in patients with autosomal recessive non-syndromic hearing loss

INTRODUCTION Oxidative stress plays a key role in the formation of age-related, noise-induced and drug-induced hearing loss. Thiols are organic compounds which can react with free radicals to protect against tissue and cell damage caused by reactive oxygen. There are no studies in literature on the association between autosomal recessive non-syndromic hearing loss(ARNSHL) including GJB2 and non-GJB2 mutations and thiol-disulphide balance. In this study, we aim to assess whether thiol-disulphide balance is disrupted in patients with ARNSHL. METHODS Thirty-one ARNSHL patients and thirty-one healthy controls were included in this study. Patients whose parents were first degree cousins and who had at least two congenital hearing loss in the same family were included in the study. Audiological tests included air - bone pure tone audiometry and auditory brain stem response. GJB2 gene analysis was performed using sanger sequence method. Tests of thiol/disulphide homeostasis were conducted using the automated spectrophotometric method. We first investigated whether there was a significant difference between ARNSHL patients and healthy controls. Then, in order to determine the differential effect of the GJB2 gene mutations and non-GJB2 gene mutations on the thiol-disulphide balance, subjects were divided into three groups: Group 1 included patients with GJB2 mutations; Group 2 included patients with non-GJB2 mutations; Group 3 included healthy subjects. RESULTS Patients with ARNSHL had significantly higher native thiol (411.6 ± 54.3 μmol/l vs. 368.0 ± 64.3 μmol/l, p = 0.006), total thiol levels (440.3 ± 56.2 μmol/l vs. 402.4 ± 65.9 μmol/l, p = 0.018), and lower disulphide levels (14.3 ± 5.7 μmol/l) vs. (17.1 ± 4.9 μmol/l), (p = 0.043) compared to the control group. Moreover, disulphide /native thiol (p < 0.001) and disulphide/total thiol (p < 0.001) were also detected lower in the ARNSHL group compared to the control group. Thiol-disulphide hemostasis parameters between all three groups showed that the native thiol and total thiol were increased in the Group 1 and Group 2. The disulphide levels decreased in Group 1 and 2, although not statistically significant. CONCLUSION It was shown that thiol levels increased and disulphide levels decreased in patients with autosomal recessive non-syndromic hearing loss. It also may suggest that there is a reverse association between ARNSHL and oxidative stress. Further studies are needed on whether or not ARNSHL cause oxidative stress limited to the inner ear and cochlea.

PEX10-related autosomal recessive cerebellar ataxia with hearing loss

Peroxisomes are present in all cells with a nucleus and contain many different enzymes. Peroxisomes have an important role in the degradation of fatty acids, the deactivation of free oxygen radicals, the biosynthesis of other lipids, and many other biochemical events. Peroxisomal biogenesis alteration has serious consequences such as severe global neurological involvement, a variable severity of dysmorphism, retinitis pigmentosa, sensorineural deafness, liver disease, and other systemic features, including death in infancy or early childhood [1]. We report two siblings with cerebellar atrophy, slowly progressive ataxia, neuropathy, and hearing loss. In both patients, novel pathogenic variant in peroxisome biogenesis factor 10 (PEX10) gene was found.

Interstitial deletion 5p14.1-p15.2 and 5q14.3-q23.2 in a patient with clubfoot, blepharophimosis, arthrogryposis, and multiple congenital abnormalities

Interstitial deletions of the short and long arms of chromosome 5 are rare cytogenetic abnormalities. The 5p distal deletion is a genetic disorder characterized by a high‐pitched cat‐like cry, microcephaly, epicanthal folds, micrognathia, severe intellectual disability and motor delays. Previously, more than 46 patients with the 5q deletion have been reported. Here, we report de novo interstitial deletions involving 5p14.1–p15.2 and 5q14.3–q23.2 in a patient with multiple congenital abnormalities, including blepharophimosis, arthrogryposis, short neck, round face, pelvic kidney, agenesis of the corpus callosum, and clubfoot. The deletions were characterized using GTG banding and aCGH microarray analysis. Concurrent 5p and 5q interstitial deletions in humans have not been previously reported. We also discussed the relationship between the 5q deleted region and clubfeet.

A novel PTCH1 gene mutation in a pediatric patient associated multiple keratocystic odontogenic tumors of the jaws and Gorlin–Goltz syndrome

Gorlin–Goltz syndrome (GGS) is an uncommon autosomal dominant inherited disorder which comprises the triad of basal cell carcinomas (BCCs), odontogenic keratocysts, and musculoskeletal malformations. Besides this triad, neurological, ophthalmic, endocrine, and genital manifestations are known to be variable. It is occasionally associated with aggressive BCC and internal malignancies. This report documents a case of GGS with a novel mutation in the PTCH1 gene in an 11-year-old child. The clinical, radiographic, histopathologic and molecular findings of this condition, and treatment are described, and a review of GGS was carried out.