Asude Durmaz

A Severe α Thalassemia Case Compound Heterozygous for Hb Adana in α1 Gene and 20.5 kb Double Gene Deletion

We report a 6-year-old boy diagnosed as transfusion dependent chronic nonspherocytic hemolytic anemia since 40 days old. Hemoglobin H inclusions were detected with brilliant cresyl blue preparation. His parents were found to be normal on physical examination. His mother had hemoglobin level of 9.34 g/dL, accompanied by typical thalassemic changes of the red cells, and inclusion bodies were also detected with brilliant cresyl blue staining. His father had normal hemoglobin level and borderline red cell indices. Mutation analysis using strip assay capable of detecting 22 mutations within the alpha genes was performed for the proband and the parents which revealed that the case was compound heterozygous for Hb Adana in alpha1 gene and 20.5 kb double gene deletion. The father was found to be heterozygous for Hb Adana alpha1 gene whereas the mother was found to be compound heterozygous for 20.5 kb double gene deletion and 3.7 kb single gene deletion. It is well known that non deletional forms of HbH disease are more severe than the deletional forms. This case represents another example of the nondeletional mutation underlying Hb Adana, which is rarely seen in alpha1 gene, and illustrates the distinctive phenotypes of both the deletional and nondeletional forms of hemoglobin H disease within the same family.

The Association of minor congenital anomalies and childhood cancer.

Although the association of some congenital malformations and specific genetic syndromes is well understood, the association between minor anomalies and cancer is not well known. In recent years some researchers have reported studies establishing this association in different types of cancer. In this study, we aimed to investigate the prevalence and patterns of age‐independent minor anomalies in childhood cancer patients.

Evolution of Genetic Techniques: Past, Present, and Beyond

Genetics is the study of heredity, which means the study of genes and factors related to all aspects of genes. The scientific history of genetics began with the works of Gregor Mendel in the mid-19th century. Prior to Mendel, genetics was primarily theoretical whilst, after Mendel, the science of genetics was broadened to include experimental genetics. Developments in all fields of genetics and genetic technology in the first half of the 20th century provided a basis for the later developments. In the second half of the 20th century, the molecular background of genetics has become more understandable. Rapid technological advancements, followed by the completion of Human Genome Project, have contributed a great deal to the knowledge of genetic factors and their impact on human life and diseases. Currently, more than 1800 disease genes have been identified, more than 2000 genetic tests have become available, and in conjunction with this at least 350 biotechnology-based products have been released onto the market. Novel technologies, particularly next generation sequencing, have dramatically accelerated the pace of biological research, while at the same time increasing expectations. In this paper, a brief summary of genetic history with short explanations of most popular genetic techniques is given.

Molecular analysis and clinical findings of Griscelli syndrome patients.

Griscelli syndrome (GS) is a rare autosomal recessive disorder associated with skin or hair hypopigmentation, hepatosplenomegaly, pancytopenia, and immunologic and central nervous system abnormalities. GS type II is caused by RAB27A mutations. We present RAB27A mutation analysis of 6 cases diagnosed as GS type II. Missense mutations (L26P and L130P) in 2 cases, deletion of 5 bases (514delCAAGC) in 2 cases, and 1 base deletion (148delA) in 2 cases were detected. This report has importance in phenotype-genotype correlation of different types of mutations including missense mutations and deletions within the RAB27A gene in GSII syndrome.

The Rate of Sex Chromosome Aneuploidies in Prenatal Diagnosis and Subsequent Decisions in Western Turkey

AIMS Sex chromosome abnormalities (SCAs) are the most common genetic disorder with a frequency of 1/400 or 1/500 live births. In this study we aimed to evaluate the initial indications, frequencies, and pregnancy termination rates of pregnancies with SCAs referred to Ege University Medical Faculty, Department of Medical Genetics. Prenatal diagnosis was performed in 7505 cases in the period of January 1998 through December 2009. RESULTS In this study, their initial indications and fetal karyotype results were evaluated retrospectively. A total of 60 pregnancies (0.80%) with SCA were evaluated. Turner syndrome was the most commonly diagnosed SCA in prenatal diagnosis (60%). The most common referral reason for pregnancies with Turner syndrome was cystic hygroma on ultrasonography. Of 14 pregnancies having a prenatal diagnosis with SCA (Turner syndrome: 7, Klinefelter syndrome: 5, Mosaic Turner syndrome: 2), 12 with SCA (85.7%) were terminated. The ratio of SCA in the prenatally diagnosed cases was similar to those reported in the literature. Although the ratio of terminated pregnancies with Turner syndrome was similar to those reported from European countries, all the pregnancies with Klinefelter syndrome have chosen termination, which showed a regional difference in Turkey. CONCLUSION It is important to consider the decisions of the families during the genetic counseling sessions of the couples having SCAs.

Interview with Parents of Children with Down Syndrome: Their Perceptions and Feelings

ObjectiveTo obtain information about the life of the families having children with Down Syndrome through an interview with parents. The authors focused on the effect of having a child with Down syndrome on the parents, factors causing problems on the family and the characteristics of a family with children having Down syndrome.MethodsIn the present study, the authors evaluated the social, economic and individual problems of the parents (n = 100) who had a child with DS by an interview consisting of 16 questions about the families’ characteristics, their relations with each other and other people and their attitudes towards the child with DS . The control group consisted of 100 subjects having healthy children who were recruited from the outpatient clinics of the same hospital.ResultsThe authors found that children with DS mostly spend their time with their mothers, and mothers reported higher levels of stress than fathers. The rate of mothers who reported higher possibility to divorce in the future is much higher than fathers (p < 0.05).ConclusionsHigh rates of marital and parental problems, particularly perceived by the mothers, observed in this study are the main issues which should be considered during the assessment of those children in order to cope with the problems and improve both patients’ and families’ life quality.

Evaluation of the miRNA profiling and effectiveness of the propolis on B-cell acute lymphoblastic leukemia cell line

Acute lymphoblastic leukemia (ALL) is one of the most frequent causes of death from cancer. Since the discovery of chemotherapeutic agents, ALL has become a model for improvement of survival. In parallel to this, serious side effects were observed and new natural therapeutic options has been discussed. One of these substances is called propolis which is a resinous substance gathered by honeybees. In the molecular era, miRNAs have been shown to play crucial roles in the development of many clinical conditions. The aim of this study is to evaluate the effect of Aydın propolis on 81 human miRNA activity in CCRF-SB leukemia cell line. Apoptotic effects of propolis on cell lines were also evaluated and apoptosis were found to be induced 1.5 fold in B-cell leukemia cells. The expression of 63 miRNAs (46 miRNAs were downregulated, 19 miRNAs were upregulated) in propolis treated leukemia cells have changed significantly (p<0.05). In conclusion propolis has changed expression of miRNAs which have epigenetic effects on leukemic cells. It is thought that it can be a promising agent for ALL treatment for future studies.

Demonstration of Uniparental-Isodisomy on Chromosome 22q11.2 in a Patient With Childhood Schizophrenia and Facial Dysmorphology by Whole-Genome Analysis

Case Report An 8-year-old girl was referred because of mental retardation and behavioral problems. Written, informed consent was obtained from the parents for the publication of the patient’s details. She was born to consanguineous parents at 31–32 weeks’ gestation. Her birth percentiles were in normal ranges. Her developmental milestones were slightly delayed. There was no history of psychiatric disorder in the relatives except that there were two members with idiopathic mental retardation. Her physical assessment at age 8 revealed elfin-like facial features, sparse medial eyebrows, arched eyebrows, hypertelorism, depressed nasal bridge, bulbous nasal tip, downturned corners of mouth, thick lower lip, and joint laxity. Imaging studies were normal. Psychiatric evaluation at age 3 revealed language-development delay, restricted social relationships, echolalia, and lack of interest in peer-relationships and toys. Her psychometric evaluation with developmental tests showed a 1-year delay. Echolalia, social-relationship restrictions, and not having imaginary play were noted as autistic-like features. At age 6, unrealistic fears, psychomotor agitation, disorganized behavior, auditory and visual hallucinations, incoherence, irrelevant and disorganized speech, and delusions were observed. She was diagnosed as “very-earlyonset schizophrenia” according to the DSM-IV criteria. Her Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) scores were 75 and 72, respectively. Her psychiatric disorder severity score was 6, according to Clinic Global Impression Scale–Severity (CGIS–S). Her karyotype and FISH analysis were normal. Whole-genome analysis by Affymetrix Human SNP Assay 6.0 kit revealed inherited copy-number variations (CNVs) and loss-of-heterozygosity (LOH) on a number of regions, which could be due to the parental consanguinity. LOH on chromosome 22 cent-q11.2 spanned 6 Mb. CNV analysis showed no evidence of any deletion in this region. The same analysis for the parents was normal. Microsatellite marker analysis with 8 markers confirmed maternally-inherited UPD (Figure 1). Catechol-O-methyltransferase (COMT) gene at 22q11, which has been identified as a susceptibility locus for schizophrenia, revealed 100-fold down-regulation, as compared with a control group. Therefore, it could be speculated that COMT could be one of a number of other genes down-regulated in this UPD region that may have contributed to the clinical presentation. In conclusion, this is the first report reinforcing the link between FIGURE 1. Microsatellite Marker Analysis of the Family (microsatellite markers in the UPD region are highlighted in gray) LETTERS

Early-Onset Isolated Bilateral Pheochromocytoma As a Major Clinical Manifestation of von-Hippel Lindau Syndrome Type 2C

48 ©Copyright 2018 by Ege University Faculty of Medicine, Department of Pediatrics and Ege Children’s Foundation The Journal of Pediatric Research, published by Galenos Publishing House. Ad dress for Cor res pon den ce Ayhan Abacı MD, Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, İzmir, Turkey Phone: +90 232 412 60 76 E-mail: ayhanabaci@gmail.com ORCID ID: orcid.org/0000-0002-1812-0321 Re cei ved: 23.11.2016 Ac cep ted: 13.12.2016 1Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, İzmir, Turkey 2Ege University Faculty of Medicine, Department of Medical Genetics, İzmir, Turkey 3Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Intensive Care Unit, İzmir, Turkey 4Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, İzmir, Turkey 5Dokuz Eylül University Faculty of Medicine, Department of Pediatric Surgery, İzmir, Turkey Sezer Acar1, Hale Tuhan1, Korcan Demir1, Ayça Aykut2, Asude Durmaz2, Ünal Utku Karaarslan3, Gözde İnci4, Oğuz Ateş5 Ece Böber1, Ayhan Abacı1

Two childhood pheochromocytoma cases due to von Hippel -Lindau disease, one associated with pancreatic neuroendocrine tumor; a rare manifestation

von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited disorder, characterized by hemangioblastomas of the retina and central nervous system (CNS); renal cysts; clear cell carcinoma; pheochromocytoma (PCC); endolymphatic sac tumors; cystadenomas of the epididymis in males; broad ligament of uterus in females; pancreatic cysts; cystadenomas; and neuroendocrine tumors. We report two cases of VHL disease that presented with PCC as the first manifestation. Further clinical developments during follow-up, hemangioblastoma of CNS in one case and a pancreatic neuroendocrine tumor (PNET) in the second case led to the diagnosis of VHL disease. Genetic analyses of the two cases revealed p.Arg161Gln (c.482G>A) and p.Leu129Pro (c.386T>G) heterozygous missense mutations in the VHL gene, respectively. In children, PCC may be the only and/or initial manifestation of VHL with delayed manifestations of the syndrome in other organs. PNET is a very rare manifestation of VHL disease. To the best of our knowledge, this is only the second reported case presenting with a combination of a PNET and bilateral PCC as components of childhood VHL disease. Pediatric patients diagnosed with PCC should be investigated for genetic causes and especially for VHL.