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Background: Alzheimer’s disease is a multifactorial, neurodegenerative disease which is considered the most common cause of dementia. It is divided into two subtypes based on the age of onset: Early-Onset Alzheimer’s Disease (EOAD) and Late-Onset Alzheimer’s Disease (LOAD). Objective: In this study, we aimed to analyse the polymorphisms of APOE2/E3/E4, ACE I/D, PICALM rs3851179, which are thought to increase the risk of disease, and CYP2D6 rs1080985, that affects the therapy response. Methods: 102 early onset and 99 late onset Alzheimer's patients diagnosed according to DSM-IV and NINCDS-ADRDA diagnostic criteria were included in the study. MMSE test was applied at the time of diagnosis and the control examination was performed after 6 months. We analysed the polymorphisms of APOE2/E3/E4 by fragment analysis and ACE I/D, PICALM rs3851179, CYP2D6 rs1080985 by Real Time- PCR. The response of the therapy and effects on prognosis were compared between groups by Mini-Mental State Exam test scores. Results: The score differences of the women were significantly lower than men’s score differences. The score differences of the EOAD group were significantly lower than the LOAD group in women. Family history situation was higher in men compared to women. The score differences were higher at CC genotype for PICALM rs3851179 in the EOAD group; the score differences were higher at E3/E4 genotype than E2/E2 genotype in LOAD. Also, the score differences were significantly higher at PICALM rs3851179 in the acetylcholinesterase inhibitor+antidepressant therapy group. Conclusions: The relationship between the treatment groups and related gene regions was investigated extensively for the first time in the literature. As a result, it will be a guide in the clinic in light of the findings of the prognosis and pharmacogenetic interactions of the disease obtained from the study.

Early pregnancy loss is the outcome of approximately 10% of clinically recognized pregnancies and chromosomal abnormalities are the underlying reason in 50%. In this report we discussed aneuploidy mechanisms and management options based on a couple with recurrent aneuploidies. Thirty-five-year-old female was referred with spontaneous abortion. Quantitative Fluorescent PCR was consistent with trisomy 21 but karyotyping revealed double trisomy of 48,XY,+7,+21. During follow-up, another abortion was diagnosed as 47,XX,+16. Peripheral blood analysis revealed a borderline mosaic 46,XX[95]/45,X[5] karyotype. Her physical examination was normal but abdominal ultrasonography revealed accessory spleen and double ureter in left kidney. We excluded Robertsonian translocations, structural aberrations or trisomic mosaicism as a cause but the borderline 45,X mosaicism may be the triggering factor by decreasing oocyte reserve. Presence of urinary malformation indicates that genitourinary mosaicism may be higher, although ovarian biopsy cannot be performed to determine it. Genetic counseling is vital in management of such cases., Erken gebelik kaybı, klinik gebeliklerin yaklaşık %10'unun sonucudur ve kromozomal anomaliler en az %50'sindeki temel nedendir. Bu yazıda ardışık düşüklerde farklı anöploidiler saptanan bir olgu üzerinden anöploidi mekanizmaları ve takipte düşünülmesi gereken seçenekler tartışılmıştır. Otuz beş yaşında kadın spontan abortus ile başvurdu. Kantitatif floresan PCR, trizomi 21 ile uyumluydu. Ancak kültür süreci sonunda yapılan karyotipleme 48,XY,+7,+21 çift trizomisini ortaya çıkardı. Olgunun takibinde başka bir düşük 47,XX,+16 olarak saptandı. Periferik kandan sitogenetik analizinde sınırda mozaik 46,XX[95]/45,X[5] karyotipi görüldü. Fizik muayenesi normaldi fakat abdominal ultrasonografide sol böbrekte çift üreter ve aksesuar dalak mevcuttu. Tekrarlayan trizomilerin olası nedenlerinden Robertsonian translokasyonlar, yapısal anomaliler veya trizomi mozaikliği dışlandı. Düşük oranlı 45,X mozaikliği ise oosit rezervini azalttığından riski arttırabilir. Olgudaki malformasyonlar mozaikliğin genitoüriner sistemde daha yüksek oranlı olabileceğini göstermektedir. Over biyopsisi invaziv doğası nedeniyle yapılamadığından bu oranının bilinmesi mümkün değildir. Tanı ve tedavi seçeneklerinin sınırlı kaldığı benzer vakaların yönetiminde genetik danışma hayati öneme sahiptir.

Objective: To find out if Charcot–Marie–Tooth (CMT) patients, who have peripheral vestibular as well as peripheral somatosensory impairment, have worse postural balance than those who do not. Methods: We studied 32 patients with various CMT phenotypes and genotypes. Vestibular function was measured with the video head impulse test (vHIT) which tests vestibulo-ocular reflex (VOR) gain from each of the six semicircular canals in response to rapid head rotations. Postural balance was evaluated with a battery of four postural tests with emphasis on the modified clinical test of sensory integration in balance (mCTSIB). Results: Half of the 32 patients had some impairment of vestibular function ranging from mild, affecting only 1–2 semicircular canals, to almost total affecting all 6 semicircular canals. Their mCTSIB scores correlated with VOR gain from the vertical rather than from the lateral semicircular canals. The worse the vertical VOR gain the worse the mCTSIB score. Conclusion: We propose that any CMT patient could have clinically inapparent vestibular impairment that can be easily measured with the vHIT. This vestibular impairment could be contributing to their imbalance and could respond to a focused vestibular rehabilitation program. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature., 216S658 Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK, Study funded by the Scientific and Technological Research Council of Turkey (TÜBİTAK) under Grant no. (216S658). Acknowledgements

Background The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations. Objective To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population. Methods Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin (FXN) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole-exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype. Results Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix-Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole-exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty-eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data. Conclusion With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. (c) 2021 International Parkinson and Movement Disorder Society, Suna and Inan Kirac Foundation; Koc UniversityKoc University; Bogazici UniversityBogazici University, This work was supported by funds from Suna and Inan Kirac Foundation, Koc University, Bogazici University.

To find out if Charcot-Marie-Tooth (CMT) patients, who have peripheral vestibular as well as peripheral somatosensory impairment, have worse postural balance than those who do not.We studied 32 patients with various CMT phenotypes and genotypes. Vestibular function was measured with the video head impulse test (vHIT) which tests vestibulo-ocular reflex (VOR) gain from each of the six semicircular canals in response to rapid head rotations. Postural balance was evaluated with a battery of four postural tests with emphasis on the modified clinical test of sensory integration in balance (mCTSIB).Half of the 32 patients had some impairment of vestibular function ranging from mild, affecting only 1-2 semicircular canals, to almost total affecting all 6 semicircular canals. Their mCTSIB scores correlated with VOR gain from the vertical rather than from the lateral semicircular canals. The worse the vertical VOR gain the worse the mCTSIB score.We propose that any CMT patient could have clinically inapparent vestibular impairment that can be easily measured with the vHIT. This vestibular impairment could be contributing to their imbalance and could respond to a focused vestibular rehabilitation program.

A 12-year-old girl with bilateral stage 2B Coats disease was screened meticulously for a possible underlying systemic disease as she was female and the disease was bilateral. Full systemic workout turned out to be unremarkable. However, an ABCA4 gene mutation was found in the genetic analysis. NDP and TINF2 gene mutations were not present. She was successfully treated with a bilateral, single intravitreal injection of dexamethasone implant and a single session of indirect laser photocoagulation with a relatively good anatomic and functional result. To the best of our knowledge, the present case is the only reported case of Coats disease with an ABCA4 gene mutation. (C) 2018 The Author(s) Published by S. Karger AG, Basel

Objective: The objective of the present study was to describe the phenotypic features of Turner syndrome (TS) and to investigate the relationship between the genotype and the phenotype.

Purpose: 22q11.2 deletion syndrome is a contiguous gene deletion syndrome with multisystem involvement characterized by cardiac defects, immunodeficiency and hypocalcemia. Variable expression and a wide range of clinical findings make it difficult for clinicians to decide on the test. Methods: Evaluation was made of the clinical findings of patients who underwent the FISH test for 22q11.2 deletion syndrome between 2006 and 2017. Results: Of the 180 patients, 152 84.45% had cardiac defects, 5 2.78% had immune defects, 132 73.4% had dysmorphic findings and 52 28.89% had growth / developmental delay. Ten patients had 22q11.2 deletion syndrome 5.56% and 9 of these had cardiac defects. Hypocalcemia was present in 5 50% patients and only one patient had immunodeficiency. Conclusion: In this study, the accuracy of the indication was evaluated retrospectively based on the clinical findings of patients who underwent FISH analysis for 22q11.2 deletion syndrome. In cases with congenital cardiac defects, although 22q11.2 deletion syndrome is one of the possible diagnoses of the clinician, a detailed examination of the defect type before testing will increase the diagnosis rate. It should be kept in mind that this syndrome should be considered in the presence of major findings such as immunodeficiency or hypocalcemia

Aim: We aimed to share our genetic test results for SMA since 2001, and compare the commonly used screening and diagnostic methods for SMA.

The case presented here describes a female patient with recurrent miscarriages and a normal microarray analysis result. However, the coexistence of a robertsonian (21;21) translocation and complementary mosaic ring chromosome 21 was detected by karyotyping and FISH analysis. Partial trisomy 21 was found with QF-PCR and microarray analysis in one of the fetuses. The aim of this report was to emphasize the diagnostic importance of conventional cytogenetics. (C) 2019 S. Karger AG, Basel

Thanatophoric dysplasia is one of thenewborn’s dwarfism syndromes usually resulting in death during perinatal periodand manifesting as short extremities. It is characterized by macrocephaly,prominent forehead, narrow thorax, short extremities, flattened vertebralbodies, curved femurs. This is caused by mutations in the fibroblast growthfactor receptor 3 (FGFR3) gene andshows autosomal dominant inheritance model. In this report, we presented a casewith abnormal USG findings during perinatal period and detected to carry ap.R248C mutation in FGFR3 gene inamniosynthesis fluid., Tanatoforik displazi, genelde perinataldönemde ölümle sonuçlanan ve kısa ekstremiteler ile kendini gösterenyenidoğanın cücelik sendromlarından biridir. Makrosefali, belirgin alın, dartoraks, vertebralarda düzleşme, ekstremitelerde kısalık, femurda eğrilme ilekarakterizedir. Fibroblast büyüme faktörü reseptörü 3 (FGFR3) genindeki mutasyonlardan kaynaklanır ve otozomal dominantkalıtım modeli gösterir. Bu makalede, prenatal dönemde anormal USG bulgularıolan, amniyosentez materyalinden yapılan FGFR3gen analizi ile p.R248C mutasyonu saptanan bir olgu anlatılmıştır.

Objectives: We have no series report concerning genetic etiology of Alport Syndrome AS in our country. So, we aimed to investigate AS related pathogenic variants of COL4A3, COL4A4 and COL4A5 genes in index cases and their families who referred to our center.Patients and Methods: The study includes 32 subjects 17 index cases and their relatives who are investigated between years 2018-2019 by NGS targeting the coding regions of related genes. The test results and clinical findings of the cases are studied retrospectively.Results: By the presented study, 19 individuals identified to have COL4A3 and COL4A5 variations which could be important for the clinical management. In four cases, there are novel variants. In two cases, there are digenic variations. There is no clinically relevant variant in COL4A4 gene. The most frequent three mutations of COL4A5 gene reported in United States US are not determined in our study group.Conclusion: The diagnostic genetic tests of AS should be designed to include whole coding regions of COL4A3 and COL4A5 genes, not just for the frequently reported pathogenic variants. The cases without pathogenic variants by sequencing should be investigated for deletions/duplications of COL4A5 gene. Clinical findings of our cases with novel genetic variants are presented as a contribution to literature

Introduction By looking through our ethical committee cases, we demonstrate the main arguments we use for making a judgment in face of fetal abnormalities. Our decision making model is a simplified algorithm of the arguments and concepts we use in scientific-ethic discussion. Materials and Methods A retrospective analysis was conducted from single, tertiary referral center of patients evaluated for fetal abnormalities from 2004 to 2014. We hypothesized that all our judgments would fit into a decision-tree model. Results 553 fetal abnormality cases were discussed, 348 (63%) were given termination of pregnancy (TOP) proposal. When detected

Objectives: This study aims to investigate the clinical impact of the R202Q (c.605G>A) alteration of Mediterranean fever (MEFV) gene in children with familial Mediterranean fever (FMF). Patients and methods: Medical records of 115 patients (51 males, 64 females; mean age 6.6±3.8 years; range 8 months to 15.8 years) presenting with FMF pre-diagnosis were examined. Patients were classified into two groups based on number of mutated alleles (one-mutant allele and twomutant alleles), and these groups were classified into three subgroups (Group 1; subgroup 1: M694V/R202Q, subgroup 2: M694V/other, subgroup 3: other/other, and Group 2; subgroup 4: R202Q/-, subgroup 5: other/-, subgroup 6: -/-). Sex, age, abdominal pain, fever, arthritis or arthralgia, myalgia, erysipelas-like erythema, chest pain, amyloidosis, family history of FMF, and definitive FMF frequency were compared between groups. Results: The most common allele alterations were the heterozygous R202Q alteration (27%) and the compound heterozygous mutation M694V/ R202Q (20.9%). The R202Q alteration of MEFV gene was detected in 76 patients (66%) (15 homozygous). There was non-M694V (E148Q, V726A) mutation in two of these patients. One (50%) of the patients with isolated R202Q homozygous alteration and six (19%) of the patients with isolated R202Q heterozygous alteration had definitive FMF. In the two-mutant allele group; abdominal pain, fever, arthritis/arthralgia, and definitive FMF frequency were lower in subgroup 1 than subgroup 2. There was no significant difference in clinical findings and definitive FMF frequency between subgroup 2 and subgroup 3. In the one-mutant allele group, clinical findings did not differ between subgroups. Conclusion: R202Q alteration of the MEFV gene may lead to symptoms consistent with FMF. However, R202Q/M694V compound heterozygosity is more associated with mild phenotype than compound heterozygous mutation of M694V.

Aims This study aimed to investigate sleep patterns, sleep disturbances and possible factors that are associated with sleep disturbances among children with familial Mediterranean fever (FMF). Patients and methods Fifty-one patients with FMF and 84 age- and sex-matched healthy controls were enrolled in the study. The patients who had an attack during the last 2 weeks were not included. Demographic data, FMF symptoms, disease duration, dose of colchicine, disease severity score, number of attacks in the last year, MEFV mutation and serum C-reactive protein (CRP) levels were recorded for each patient. A Children's Sleep Habits Questionnaire was performed. Results The total sleep scores of the patients with FMF were significantly higher than the control group. Total sleep durations were similar between FMF patients and controls. Children with FMF had significantly higher scores regarding sleep-onset delay, sleep anxiety, night wakings and sleep-disordered breathing when compared to healthy controls. There was a significant positive correlation between number of attacks in the last year and sleep onset delay, night wakings and sleep disordered-breathing. Disease severity score and CRP levels were not associated with any of the subscale scores. The patients with exertional leg pain had significantly higher total sleep scores than the ones without. Furthermore, patients with exertional leg pain had significantly higher subscale scores regarding sleep onset delay, parasomnias and sleep-disordered breathing. Conclusion This study showed for the first time that children with FMF had more sleep disturbances than their healthy peers. Higher numbers of attacks and exertional leg pain were associated with poor sleep quality. In conclusion, this study underlines the need to assess and manage sleep problems in children with FMF.

WOS: 000418562600010, PubMed ID: 29278518, Genital anomalies, ranging from female genitalia to milder degrees of undervirilization, are rarely reported in Klinefelter syndrome, in which a male is classically expected to be born with male external genitalia. Though androgen insensitivity syndrome (AIS) is one of the possible pathogenic mechanisms also in Klinefelter syndrome with genital anomalies, to date the AR gene has not been analyzed in any of the published cases of Klinefelter syndrome of the milder phenotype, except for those patients presenting with a severe phenotype, such as female external genitalia. Lack of interest in considering androgen insensitivity in Klinefelter syndrome with a milder phenotype of genital anomalies may impede its identification through an accurate diagnosis. We present a 14-month-old boy with penoscrotal hypospadias, micropenis, and a ventral penile chordee abnormality who was observed to have both a 47, XXY karyotype and a known missense mutation in the AR gene that was inherited from his mother. Although it is recommended that Klinefelter syndrome be considered in the differential diagnosis of penoscrotal abnormalities, mutations in specific genes involved in androgen synthesis or responsiveness should also be investigated.

Objective: To survey experience with the first-trimester combined test (FCT) for trisomy 21 (T21) in different risk score groups to determine the most useful clinical application of cell-free fetal DNA (cffDNA) screening. Methods: In a retrospective study, the records of FCT results obtained at a center in Turkey between January 2009 and January 2014 were reviewed. The FCT results and rates of uptake of invasive diagnostic testing were compared among different risk score groups. Results: FCT results were available for 4804 pregnancies; 276 (5.7%) had IDT results. Ten (72.7%) of 11 cases of T21 had a risk score of 1:300 or more. The IDT uptake rates were 54.5%, 51.9%, and 47.4% at risk scores of 1:100 or more, 1:200 or more, and 1:300 or more, respectively. In the group at intermediate risk (1:1001-1:3000), no pregnancy had an FCT result of both low pregnancy associated plasma protein A and high free beta-human chorionic gonadotropin, but 30 (3.9%) of 766 pregnancies had both advanced maternal age and high beta-human chorionic gonadotropin. Conclusion: cffDNA screening should be used to optimize IDT uptake in pregnancies with a risk score of 1:101-1:1000. The selective power of the FCT diminishes beyond the 1:1001 score and cffDNA screening cannot yet be recommended routinely. (C) 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

By looking through our ethical committee cases, we demonstrate the main arguments we use for making a judgment in face of fetal abnormalities. Our decision making model is a simplified algorithm of the arguments and concepts we use in scientific-ethic discussion.A retrospective analysis was conducted from single, tertiary referral center of patients evaluated for fetal abnormalities from 2004 to 2014. We hypothesized that all our judgments would fit into a decision-tree model.553 fetal abnormality cases were discussed, 348 (63%) were given termination of pregnancy (TOP) proposal. When detected24 weeks, fetuses with chromosomal abnormality/genetic disorders (n:100) and with mental retardation risk (n:93) ended up with TOP proposal. For incompatibility with life cases (n:111) and the multimorbidity cases (n:44) the committee suggest TOP, regardless of gestational age. The highest family approval ratios were in chromosomal abnormalities/genetic disorders group (93%), and the lowest figures were in mental retardation risk group (80%).Continuously changing literature on prenatal and postnatal therapy options and the long term outcome of various fetal abnormalities influence committee decisions. Theoretical high success rates and inconsistent data on long term prognosis of some anomaly groups resulted in heterogenous decisions and various approval ratios.

To elucidate the genetic factors causing clinical differences in the children with Down syndrome and evaluate possible maternal risk factors, the researchers have investigated GSTM1, GSTT1, GSTP1 gene polymorphisms. Four groups were defined: group I (n = 52), children with Down syndrome; group II (n = 70), healthy children; group III (n = 52), mothers of the children with Down syndrome; and group IV (n = 69), mothers of the healthy children. Genomic DNA was extracted from the white blood cells and GenID (R) GmbH kit used for GST MI, T1 and PI gene amplification to determine polymorphisms. The researchers did not detect any significant difference in the allele frequencies between groups I and II, nor groups III and IV. The data indicated no relationship between detected GST polymorphisms, neither with Down syndrome nor with the risk of having an infant with Down syndrome.