A Homozygous Missense Variant in HSD17B4 Identified in Two Different Families.

Background: Perrault syndrome is an inherited disorder with clinical findings that differ according to sex. It is characterized by a variable age of onset and sensorineural hearing loss in both sexes, as well as ovarian dysfunction in females with a 46,XX karyotype. Although it is a rare autosomal recessive syndrome, with approximately 100 affected individuals reported in the literature, it shows both genotypic and phenotypic variations. Mutations in the HSD17B4 gene have been identified as one of the genetic causes of Perrault syndrome. Case Presentation: A female case and a male case from two different unrelated families with a new variant in the HSD17B4 gene, which were not previously described in the literature and were accompanied by hearing loss, skeletal anomalies, and neurological symptoms, were presented. Conclusion: We defined Perrault syndrome cases in Turkey caused by a novel mutation in HSD17B4. Whole-exome sequencing is a useful diagnostic technique with varying clinical results due to genetic and phenotypic heterogeneity.

The first Turkish family with a novel biallelic missense variant of the ALKBH8 gene: A study on the clinical and variant spectrum of ALKBH8-related intellectual developmental disorders.

ABH8, the protein encoded by the ALKBH8 gene, modifies tRNAs by methylating their anticodon wobble uridine residues. The variations in the ALKBH8 gene are associated with the "intellectual developmental disorder, autosomal recessive type 71" (MIM: 618504) phenotype in the OMIM database. This phenotype is characterized by global developmental delay, facial dysmorphic features, and psychiatric problems. To date, 12 patients from five distinct families carrying variants of the ALKBH8 gene have been reported in the literature. In the present study, we report the first Turkish family harboring a novel homozygous missense variant, NM_138775.3:c.1874G > C (p.Arg625Pro), in the last exon of the ALKBH8 gene. Two affected siblings in this family showed signs of global developmental delay and intellectual disability. Based on the dysmorphological assessment of the cases, fifth finger clinodactyly and fetal fingertip pads were prominent, in addition to the dysmorphic findings similar to those reported in previous studies. Minor dysmorphic limb anomalies in relation to this phenotype have not yet been previously reported in the literature. Our computational studies revealed the potential deleterious effects of the Arg-to-Pro substitution on the structure and stability of the ABH8 methyltransferase domain. In the present report, the first Turkish family with an ultrarare disease associated with the ALKBH8 gene was reported, and a novel deleterious variant in the ALKBH8 gene and additional clinical features that were not reported with this condition have been reported.

Prediction of molecular phenotypes for novel SCN1A variants from a Turkish genetic epilepsy syndromes cohort and report of two new patients with recessive Dravet syndrome.

Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+) are both epilepsy syndromes that can be attributed to deleterious mutations occurring in SCN1A, the gene encoding the pore-forming α-subunit of the NaV 1.1 voltage-gated sodium channel predominantly expressed in the central nervous system. In this research endeavor, our goal is to expand our prior cohort of Turkish patients affected by SCN1A-positive genetic epilepsy disorders. This will be accomplished by incorporating two recently discovered and infrequent index cases who possess a novel biallelic (homozygous) SCN1A missense variant, namely E158G, associated with Dravet syndrome. Furthermore, our intention is to use computational techniques to predict the molecular phenotypes of each distinct SCN1A variant that has been detected to date within our center. The correlation between genotype and phenotype in Dravet syndrome/GEFS+ is intricate and necessitates meticulous clinical investigation as well as advanced scientific exploration. Broadened mechanistic and structural insights into NaV 1.1 dysfunction offer significant promise in facilitating the development of targeted and effective therapies, which will ultimately enhance clinical outcomes in the treatment of epilepsy.

Primary Immunodeficiencies in Children Initially Admitted with Gastrointestinal/Liver Manifestations.

Purpose: The gastrointestinal system is the most commonly affected organ, followed by the lungs, in patients with primary immunodeficiency disease (PID). Hence, it is common for children with PIDs to present with gastrointestinal symptoms. We aimed to analyze the clinical and histopathological findings of patients who were initially admitted to pediatric gastroenterology/hepatology clinics and subsequently diagnosed with PIDs to identify the clinical clues for PIDs. Methods: The demographic, laboratory, and histopathological findings, treatment modality, and outcomes of patients initially admitted to the pediatric gastroenterology/hepatology unit and subsequently diagnosed with PIDs were recorded. Results: The study included 24 patients (58.3% male; median age [range]: 29 [0.5-204] months). Common clinical presentations included chronic diarrhea (n=8), colitis (n=6), acute hepatitis (n=4), and acute liver failure (n=2). The association of autoimmune diseases, development of malignant diseases, and severe progression of viral diseases was observed in 20.8%, 8.3%, and 16.6% of the patients, respectively. Antibody deficiency was predominantly diagnosed in 29.2% of patients, combined immunodeficiency in 20.8%, immune dysregulation in 12.5%, defects in intrinsic and innate immunity in 4.2%, autoinflammatory disorders in 8.3%, and congenital defects of phagocytes in 4.2%. Five patients remained unclassified (20.8%). Conclusion: Patients with PIDs may initially experience gastrointestinal or liver problems. It is recommended that the association of autoimmune or malignant diseases or severe progression of viral diseases provide pediatric gastroenterologists some suspicion of PIDs. After screening using basic laboratory tests, genetic analysis is mandatory for a definitive diagnosis.

De novo Pure Partial Trisomy 6p Associated with Facial Dysmorphism, Developmental Delay, Brain Anomalies, and Primary Congenital Hypothyroidism.

Introduction: Partial trisomy 6p is a rare chromosomal anomaly, characterized by low birth weight, developmental delay, craniofacial abnormalities, feeding difficulties, congenital heart defects, and renal abnormalities. Some of the partial trisomy 6p cases reported in the literature included partial monosomy of another chromosome. This is often due to the fact that one of the parents is a balanced translocation carrier, thereby making it difficult to determine the genotype-phenotype relationship. Pure partial trisomy 6p cases are even rarer and may occur as a result of a marker chromosome, tandem or inverted duplication, and interchromosomal insertion. Case Presentation: In this study, we evaluated the physical characteristics and genetic data of a 2-year-old girl with developmental delay and facial dysmorphic features. Dysmorphology assessment revealed the presence of a prominent forehead, short and narrow palpebral fissures, blepharoptosis, convex nasal ridge, hemangioma on the left eyelid, high-arched palate, retromicrognathia, and low-set ears. The patient‧s G-banded karyotype was 46,XX,der(2)t(2;6)(q37.3;p22.1). Upon SNP-array analysis, aimed to determine the origin of the extra chromosomal material detected in chromosome 2 of the patient, there was a de novo 27.5-Mb duplication at 6p, arr[GRCh37] 6p25.3p22.1(204,909_27,835,272)×3, interpreted to be pathogenic. Conclusion: We present this case report to clarify the clinical findings of a rare chromosomal anomaly, discuss the genes that may be related to the phenotype and contribute to the literature in terms of knowledge regarding genotype-phenotype correlation.

Genetic Landscape of SCN1A Variants in a Turkish Cohort with GEFS+ Spectrum and Dravet Syndrome.

Introduction: The α subunit of voltage-gated sodium channels in mammals is encoded by 9 different genes, and variations in the SCN1A, SCN2A, SCN3A, and SCN8A genes highly expressed in the CNS have been associated with epilepsy phenotypes. This study aimed at investigating the frequency of SCN1A gene variations in Dravet syndrome (DS) and GEFS+ spectrum phenotype cases and discussing the molecular results in the context of genotype-phenotype correlation. Methods: Fifteen patients diagnosed with DS and 54 patients meeting the GEFS+ spectrum criteria were included in this study. All patients were evaluated by next-generation sequencing and multiplex ligation-dependent probe amplification using an SCN1A gene commercial kit. Results: A total of 17 different variants were detected in 18 index cases (26%), of which 7 were novel variations (p.M1R, p.M147T, p.I767L, p.N1391Ifs*5, p.R1886G, p.E1915G, p.R1933Q). Of the 18 cases with variation in the SCN1A gene, 12 had DS and 6 had GEFS+ phenotype. The variations were de novo in all DS cases and in 1 case with a GEFS+ phenotype; in 5 GEFS+ cases, the variant was inherited from the affected parent. Discussion: This study contributes to the variation spectrum in cases with DS and GEFS+ phenotype with the novel variants detected. SCN1A genetic analysis can help in determining whether antiseizure medication should be selected or avoided in cases with variations. The elucidation of the molecular etiology makes it possible to provide the family with effective genetic counseling for future pregnancies.

Molecular characterization of Turkish patients with demyelinating Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) disease represents a distinct subgroup of inherited peripheral neuropathies with a significant prevalence throughout the world and manifests both phenotypic and genetic heterogeneity. Electrophysiological studies subclassify CMT mainly as demyelinating or axonal types. In this study, we investigated the molecular characteristics of a Turkish cohort of 23 probands out of 34 symptomatic demyelinating CMT individuals from January 2019 to December 2021. In order to identify the underlying genetic cause, we applied a rational algorithm: PMP22 gene was initially analyzed for duplication, if PMP22-duplication testing was negative, other most causative genes (GJB1, MPZ) and PMP22 were then sequenced and if no variant was detected at aforementioned tests, whole exome sequencing (WES) test was finally performed. A total of 17 patients (≅ 74%; n = 23) were found to harbor a disease-causing variant in demyelinating CMT-related genes and among the variants, PMP22-duplication was the most frequent (≅ 41%). CMT1, CMTX, and CMT4 subtypes were manifested in ten, five, and two individuals respectively. GJB1 and SBF2 genes were the only detected genes associated with the CMTs other than CMT1. We also reported totally five novel variants: c.379A > C (p.Ile127Leu) and c.548G > T (p.Arg183Leu) variants in GJB1, c.988G > T (p.Glu330Ter) variant in NEFL, c.765_770delCCCTAT (p.Pro256_Ile257del) and c.2552A > C (p.His851Pro) variants in SBF2. As the understanding of pathophysiology and molecular mechanisms of CMT continues to evolve rapidly, many therapeutic strategy options including promising small-molecular compounds, gene replacement therapy, or disease-modifying therapies will soon be implemented in the clinical setting.

Familial Hemophagocytic Lymphohistiocytosis With Heterozygous STX11 and Homozygous UNC13D Mutations Diagnosed in the Neonatal Period.

Patients with primary hemophagocytic lymphohistiocytosis may present with different mutations and phenotypic findings. It is usually presented as case reports because of its rare occurrence. Here, we discuss a case diagnosed with familial hemophagocytic lymphohistiocytosis 3, that presented in the neonatal period and was detected to have homozygous UNC13D and heterozygous STX11 mutations.

Whole-exome sequencing reveals new potential genes and variants in patients with premature ovarian insufficiency.

PURPOSE: Premature ovarian insufficiency (POI) is a heterogeneous disorder characterized by the cessation of menstrual cycles before the age of 40 years due to the depletion or dysfunction of the ovarian follicles. POI is a highly heterogeneous disease in terms of etiology. The aim of this study is to reveal the genetic etiology in POI patients. METHODS: A total of 35 patients (mean age: 27.2 years) from 28 different families diagnosed with POI were included in the study. Karyotype, FMR1 premutation analysis, single nucleotide polymorphism (SNP) array, and whole-exome sequencing (WES) were conducted to determine the genetic etiology of patients. RESULTS: A total of 35 patients with POI were first evaluated by karyotype analysis, and chromosomal anomaly was detected in three (8.5%) and FMR1 premutation was detected in six patients (17%) from two different families. A total of 29 patients without FMR1 premutation were included in the SNP array analysis, and one patient had a 337-kb deletion in the chromosome 6q26 region including PARK2 gene, which was thought to be associated with POI. Twenty-nine cases included in SNP array analysis were evaluated simultaneously with WES analysis, and genetic variant was detected in 55.1% (16/29). CONCLUSION: In the present study, rare novel variants were identified in genes known to be associated with POI, which contribute to the mutation spectrum. The effects of detected novel genes and variations on different pathways such as gonadal development, meiosis and DNA repair, or metabolism need to be investigated by experimental studies. Molecular etiology allows accurate genetic counseling to the patient and family as well as fertility planning.

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked Syndrome in Two Siblings: Same Mutation But Different Clinical Manifestations at Onset

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an early onset systemic autoimmune genetic disorder caused by mutation of the forkhead box protein 3 (FOXP3) gene. Enteropathy, endocrinopathy and skin manifestations are considered the classic triad of IPEX syndrome. However, patients with IPEX syndrome display a variety of phenotypes including life threatening multi-organ autoimmunity. Here, we present the case of two siblings with IPEX syndrome with the same hemizygous mutation, but with different types of symptomology at onset of the disease.

Early onset congenital diarrheas; single center experience.

BACKGROUND: Congenital diarrheal disorders (CDDs) are a rare group of enteropathies that typically present in the early few months of life and pose a diagnostic challenge. We aimed to analyze the clinical findings and outcome of infants with CDDs and share experience about genetic testing. METHODS: Demographic, clinical and genetic findings, and outcome of the patients (n = 24) with CDDs were recorded from hospital files. RESULTS: The onset of diarrhea was within the neonatal period in 45.8% of the patients. The most frequent causes of CDDs were defects in digestion, absorption and transport of nutrients and electrolytes (DATN) (n = 11, 45.8%) and defects in intestinal immune-related homeostasis (IIH) (n = 6, 25%). Fat malabsorption (n = 6) was the leading cause of defects in DATN. Extraintestinal manifestations including neurological involvement (25%) and renal involvement (20.8%) were common among the patients. Genetic analyses were performed for 16 patients (targeted gene analysis in 9, congenital diarrhea panel in 3, immune deficiency panel in 1 and whole-exome sequencing in 3 patients). Genetic diagnosis was achieved in 14 of 16 patients (87.5%) with therapeutic consequences in 8 of 16 patients (50%). During the follow-up, 6 patients (25%) died. CONCLUSION: The percentage of undefined etiology decreased, and treatment of the patients improved with the increased number of genetic testing in patients with CDDs.

Secondary findings in 622 Turkish clinical exome sequencing data.

CES (Clinical Exome Sequencing) is a method that we use to diagnose rare diseases with nonspesific clinical features. Besides primary indication for testing genetic information may be detected about diseases which have not yet emerged. ACMG guidelines recommend to report pathogenic variations in medically actionable 59 genes. In this study we evaluated CES data of 622 cases which were tested for various indications. According to ACMG recommendations 59 genes were screened for reportable variations. The detected variations were reviewed using distinct databases and ACMG variation classification guidelines. Among 622 cases 13 (2.1%) had reportable variations including oncogenetic, cardiogenetic disorders, and malignant hyperthermia susceptibility-related genes. In 15 cases (2.4%) heterozygous pathogenic and likely pathogenic variations were detected in genes showing autosomal recessive inheritance. Ten novel variations causing truncated protein or splicing defect were reported. We detected 11 variations having conflicting interpretations in databases and 30 novel variations, predicted as likely pathogenic via insilico analysis tools which further evaluations are needed. As to our knowledge this is the first study investigating secondary findings in Turkish population. To extract the information that may lead to prevent severe morbidities and mortalities from big data is a valuable and lifesaving effort. Results of this study will contrbute to existing knowledge about secondary findings in exome sequencing and will be a pioneer for studies in Turkish population.

Plasma microRNA levels in childhood IgA vasculitis.

INTRODUCTION: Immunoglobulin A vasculitis (IgAV) is the most common form of childhood systemic vasculitis. It is mostly self-limiting and characterized by skin, joint, gastrointestinal tract, and kidney involvement. Microribonucleic acids (miRNAs) are 18-25 base-long non-coding RNA group acting on gene expression. They have been shown to be effective on the immune system studies to date. METHOD: In our study, 24 IgAV children with skin and joint involvement and 24 healthy children were included. Five different miRNAs (miR-33, miR-34, miR-122, miR-204, and miR451) known to be expressed in plasma and related with autoimmunity pathogenesis were evaluated. miRNAs were compared between the active period of the disease, the post-treatment period, and the healthy group using the real-time PCR method. RESULTS: Expression levels of miRNA-33 and miRNA-34 increased significantly in active period of the patients compare with inactive period and control groups. The expression levels of miRNA-122 and miRNA-204 decreased significantly in active period of the patients compare with other two groups. There was no significant difference in miRNA-451 levels. CONCLUSIONS: With the experience we gained from our recent studies, we think that miRNA-204 may be a significant biomarker in autoimmune diseases. Our study is the first study between IgAV and miRNAs in children. More studies are needed to reveal this relationship. Key Points • This is the first paper to show the relationship between miRNAs and childhood IgAV. • It will provide a new perspective to evaluate the pathogenesis of the disease.

Application of Chromosome Microarray Analysis in the Investigation of Developmental Disabilities and Congenital Anomalies: Single Center Experience and Review of NRXN3 and NEDD4L Deletions.

Chromosomal microarray analysis (CMA) is a first step test used for the diagnosis of patients with developmental delay, intellectual disability, autistic spectrum disorder, and multiple congenital anomalies. Its widespread usage has allowed genome-wide identification of copy number variations (CNVs). In our study, we performed a retrospective study on clinical and microarray data of 237 patients with developmental disabilities and/or multiple congenital anomalies and investigated the clinical utility of CMA. Phenotype-associated CNVs were detected in 15.18% of patients. Besides, we detected submicroscopic losses on 14q24.3q31.1 in a patient with speech delay and on 18q21.31q21.32 in twin patients with seizures. Deletions of NRXN3 and NEDD4L were responsible for the phenotypes, respectively. This study showed that CMA is a powerful diagnostic tool in this patient group and expands the genotype-phenotype correlations on developmental disabilities.

Structural Characteristics in the γ Chain Variants Associated with Fibrinogen Storage Disease Suggest the Underlying Pathogenic Mechanism.

Particular fibrinogen γ chain mutations occurring in the γ-module induce changes that hamper γ-γ dimerization and provoke intracellular aggregation of the mutant fibrinogen, defective export and plasma deficiency. The hepatic storage predisposes to the development of liver disease. This condition has been termed hereditary hypofibrinogenemia with hepatic storage (HHHS). So far, seven of such mutations in the fibrinogen γ chain have been detected. We are reporting on an additional mutation occurring in a 3.5-year-old Turkish child undergoing a needle liver biopsy because of the concomitance of transaminase elevation of unknown origin and low plasma fibrinogen level. The liver biopsy showed an intra-hepatocytic storage of fibrinogen. The molecular analysis of the three fibrinogen genes revealed a mutation (Fibrinogen Trabzon Thr371Ile) at exon 9 of the γ chain in the child and his father, while the mother and the brother were normal. Fibrinogen Trabzon represents a new fibrinogen γ chain mutation fulfilling the criteria for HHHS. Its occurrence in a Turkish child confirms that HHHS can present in early childhood and provides relevant epidemiological information on the worldwide distribution of the fibrinogen γ chain mutations causing this disease. By analyzing fibrinogen crystal structures and calculating the folding free energy change (ΔΔG) to infer how the variants can affect the conformation and function, we propose a mechanism for the intracellular aggregation of Fibrinogen Trabzon and other γ-module mutations causing HHHS.

Assessment of Circulating Microribonucleic Acids in Patients With Familial Mediterranean Fever.

OBJECTIVES: This study aims to evaluate the plasma expression of microribonucleic acids (miRNAs) that may be associated with the pathogenesis of familial Mediterranean fever (FMF). PATIENTS AND METHODS: Thirty patients with FMF (18 males, 12 females; mean age 9.1±4.7 years; range, 3 to 15.5 years) and 30 age- and sex-matched healthy children (18 males, 12 females; mean age 9.5±4.6 years; range, 4 to 16.5 years) were included in this study. The plasma levels of four candidate miRNAs (miRNA-16, miRNA-155, miRNA-204 and miRNA-451) were measured in all subjects. The plasma levels of miRNAs were analyzed with real- time polymerase chain reaction in attack and remission periods of patients and healthy controls (HCs). RESULTS: Plasma miRNA-204 levels of FMF patients were decreased 6.5 fold in remission period compared to HCs (p<0.001). This decrease was more prominent in M694V mutation carriers. Plasma miRNA-155 levels of FMF patients were lower in remission period (p=0.03). CONCLUSION: Our findings showed significant alterations in the plasma expression of miRNA-155 and miRNA-204 in FMF patients compared to HCs. Our data suggest that miRNA-155 and miRNA-204 may be related to the pathogenesis of FMF. Further comprehensive and functional researches may help to clarify the role of miRNAs in FMF and elucidate the pathogenesis of the disease.

Constitutional Mismatch Repair Gene Defect Syndrome Presenting With Adenomatous Polyposis and Cafe au Lait Spots: A Case Report.

INTRODUCTION: Adenomatous polyps in the gastrointestinal system rarely occur in childhood and are accompanied by syndromes such as Familial adenomatous polyposis, attenuated familial adenomatous polyposis, and MUTYH-associated polyposis, Gardner and Turcot syndrome, and also mismatch repair (MMR) gene defects. In this article, we want to present a rare patient who had adenomatous polyposis and in situ carcinoma and was detected biallelic MMR gene defect. CASE: A 16-year-old female patient admitted with painless rectal bleeding, chronic abdominal pain, and anorexia for 1 year. Her physical examination was notable for multiple cafe au lait spots. The colonoscopic and histopathologic examination revealed multiple adenomatous polyps that one of them contains low-high grade dysplasia and in situ carsinoma. Genetic analysis revealed a homozygous mutation in the PMS2 gene [c.1164delT (p.H388Qfs*10) (p.His388GInfsTer10)] and she was diagnosed with constitutional MMR gene defect syndrome. Polypectomy was performed 4 times in 2 years period. Then, the patient's last colonoscopic examination revealed a large broad polyp in the rectum and multiple polyps in the other colon segments, and she underwent colectomy because of high risk of colorectal cancer. CONCLUSIONS: Adenomatous polyps are very important in childhood because of rarity. In particular, the presence of cafe au lait spots and a history of malignancy detected in relatives at an early age must be considered for CMMRD.

IL-17A, MCP-1, CCR-2, and ABCA1 polymorphisms in children with non-alcoholic fatty liver disease / Polimorfismos IL-17A, MCP-1, CCR-2 e ABCA1 em crianças com doença hepática gordurosa não alcoólica

Abstract Objective: The prevalence of non-alcoholic fatty liver disease in children has risen significantly, owing to the worldwide childhood obesity epidemic in the last two decades. Non-alcoholic fatty liver disease is closely linked to sedentary lifestyle, increased body mass index, and visceral adiposity. In addition, individual genetic variations also have a role in the development and progression of non-alcoholic fatty liver disease. The aim of this study was to investigate the gene polymorphisms of MCP-1 (-2518 A/G) (rs1024611), CCR-2 (190 G/A) (rs1799864), ABCA1 (883 G/A) (rs4149313), and IL-17A (-197 G/A) (rs2275913) in obese Turkish children with non-alcoholic fatty liver disease. Methods: The study recruited 186 obese children aged 10 -17 years, including 101 children with non-alcoholic fatty liver disease and 85 children without non-alcoholic fatty liver disease. Anthropometric measurements, insulin resistance, a liver panel, a lipid profile, liver ultrasound examination, and genotyping of the four variants were performed. Results: No difference was found between the groups in respect to age and gender, body mass index, waist/hip ratio, or body fat ratio. In addition to the elevated ALT levels, AST and GGT levels were found significantly higher in the non-alcoholic fatty liver disease group compared to the non non-alcoholic fatty liver disease group (p < 0.05). The A-allele of IL-17A (-197 G/A) (rs2275913) was associated with non-alcoholic fatty liver disease (odds ratio [OR] 2.05, 95% confidence interval: 1.12 -3.77, p = 0.02). Conclusions: The findings of this study suggest that there may be an association between IL-17A (-197 G/A) (rs2275913) polymorphism and non-alcoholic fatty liver disease development in obese Turkish children.

Resumo Objetivo: A prevalência de doença hepática gordurosa não alcoólica em crianças aumentou significativamente devido à epidemia de obesidade infantil em todo o mundo nas últimas duas décadas. A doença hepática gordurosa não alcoólica está intimamente ligada ao estilo de vida sedentário, ao aumento do índice de massa corporal e à adiposidade visceral. Além disso, variações genéticas individuais também têm um papel no desenvolvimento e na progressão da doença hepática gordurosa não alcoólica. O objetivo deste estudo foi investigar os polimorfismos genéticos MCP-1 (-2518 A/G) (rs1024611), CCR-2 (190 G/A) (rs1799864), ABCA1 (883 G/A) (rs4149313) e IL-17A (-197 G/A) (rs2275913) em crianças turcas obesas com doença hepática gordurosa não alcoólica. Métodos: O estudo recrutou 186 crianças obesas entre 10 e 17 anos, inclusive 101 crianças com doença hepática gordurosa não alcoólica e 85 crianças sem doença hepática gordurosa não alcoólica. Medidas antropométricas, resistência à insulina, painel hepático, perfil lipídico, exame ultrassonográfico do fígado e genotipagem de quatro variantes foram feitos. Resultados: Nenhuma diferença foi encontrada entre os grupos em relação à idade e sexo, índice de massa corporal, relação cintura/quadril ou proporção de gordura corporal. Além dos níveis elevados de ALT, os níveis de AST e GGT foram significativamente maiores no grupo doença hepática gordurosa não alcoólica em comparação com o grupo não doença hepática gordurosa não alcoólica (p < 0,05). O alelo A de IL-17A (-197 G/A) (rs2275913) foi associado à doença hepática gordurosa não alcoólica (odds ratio [OR] 2,05, intervalo de confiança de 95%: 1,12-3,77, p = 0,02). Conclusões: Os achados deste estudo sugerem que pode haver uma associação entre o polimorfismo IL-17A (-197 G/A) (rs2275913) e o desenvolvimento da doença hepática gordurosa não alcoólica em crianças turcas obesas.

IL-17A, MCP-1, CCR-2, and ABCA1 polymorphisms in children with non-alcoholic fatty liver disease.

OBJECTIVE: The prevalence of non-alcoholic fatty liver disease in children has risen significantly, owing to the worldwide childhood obesity epidemic in the last two decades. Non-alcoholic fatty liver disease is closely linked to sedentary lifestyle, increased body mass index, and visceral adiposity. In addition, individual genetic variations also have a role in the development and progression of non-alcoholic fatty liver disease. The aim of this study was to investigate the gene polymorphisms of MCP-1 (-2518 A/G) (rs1024611), CCR-2 (190 G/A) (rs1799864), ABCA1 (883 G/A) (rs4149313), and IL-17A (-197 G/A) (rs2275913) in obese Turkish children with non-alcoholic fatty liver disease. METHODS: The study recruited 186 obese children aged 10-17 years, including 101 children with non-alcoholic fatty liver disease and 85 children without non-alcoholic fatty liver disease. Anthropometric measurements, insulin resistance, a liver panel, a lipid profile, liver ultrasound examination, and genotyping of the four variants were performed. RESULTS: No difference was found between the groups in respect to age and gender, body mass index, waist/hip ratio, or body fat ratio. In addition to the elevated ALT levels, AST and GGT levels were found significantly higher in the non-alcoholic fatty liver disease group compared to the non non-alcoholic fatty liver disease group (p<0.05). The A-allele of IL-17A (-197 G/A) (rs2275913) was associated with non-alcoholic fatty liver disease (odds ratio [OR] 2.05, 95% confidence interval: 1.12-3.77, p=0.02). CONCLUSIONS: The findings of this study suggest that there may be an association between IL-17A (-197 G/A) (rs2275913) polymorphism and non-alcoholic fatty liver disease development in obese Turkish children.