scholarly journals A clinical case of neonatal diabetes caused by INS gene mutation

2019 ◽  
Vol 22 (2) ◽  
pp. 170-176
Author(s):  
Rosa A. Atanesyan ◽  
Tatyana A. Uglova ◽  
Tatyana M. Vdovina ◽  
Leonid Ya. Klimov ◽  
Marina U. Kostanova ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Clinical Case ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
Neonatal Diabetes ◽  
Compound Heterozygous ◽  
Pancreatic Cell ◽  
Cell Dysfunction ◽  
Genetic Examination

Neonatal diabetes mellitus (NDM) is a severe endocrine pathology diagnosed in children during the first months of life. It comprises rare (1:300 0001:400 000 newborns) metabolic disorders with postnatal pancreatic -cell dysfunction, manifested by hyperglycaemia and hypoinsulinaemia. It is currently established that molecular genetic diagnosis of neonatal diabetes forms can influence treatment and prognosis. Interestingly, most identified mutations in the insulin gene are not inherited, but are sporadic. There is evidence that, in addition to heterozygous INS mutations, NDM can be caused by homozygous or compound-heterozygous mutations. The present article presents the clinical case of a girl with NDM associated with an INS gene mutation. INS gene mutations cause permanent diabetes and require children to undergo genetic examination, especially patients with type 1 diabetes in the absence of antibodies. Currently, there are no data that allow to determine a phenotypic and genotypic portrait of NDM forms or to explain the factors determining their occurrence. Further studies of clinical cases of neonatal diabetes are therefore required to determine the characteristics of NDM subtypes with subsequent disease prognosis.

scholarly journals Werner mesomelic dysplasia

2018 ◽  
Vol 6 (4) ◽  
pp. 92-97
Author(s):  
Evgeniia A. Kochenova ◽  
Olga E. Agranovich ◽  
Svetlana I. Trofimova ◽  
Anna P. Nikitina
Keyword(s):  
Clinical Case ◽  
Regulatory Element ◽  
Molecular Genetic ◽  
Hip Dislocation ◽  
Preaxial Polydactyly ◽  
Mesomelic Dysplasia ◽  
Dominant Disease ◽  
Genetic Examination ◽  
Hands And Feet ◽  
Nasal Defects

Introduction. The term “mesomelic dysplasia” refers to a group of disorders wherein limb shortening is most pronounced in the middle segment (forearm and leg) of the extremities. Werner mesomelic dysplasia is characterized by absence or hypoplasia of the tibia, preaxial polysyndactyly on the hands and feet, as well as by triphalangeal thumbs, absence of a patella, and fibular bone dislocation. Molecular genetic causes of the disease are mutations at position 404 of the regulatory element (ZRS) of the SHH gene in the LMBR1 gene (OMIM 188740). Clinical case. A girl with triphalangeal thumbs and polydactyly of the hands, right hip dislocation, tibia hypoplasia, fibular dislocation on both sides, and preaxial polydactyly of the feet was examined and treated at the age of 1 year. Considering the clinical and radiological picture, the girl was diagnosed with Werner mesomelic dysplasia. To verify the disease, a molecular genetic examination of the child was performed. A variant of replacement of 230 T > C in the regulatory element of the ZRS of the SHH gene was discovered in the literature. Discussion. Differential diagnosis can be made with Laurin-Sandrow syndrome, which is characterized by doubling of the ulna and fibula with the absence of the radius and tibia and preaxial polydactyly/syndactyly of the hands and feet. The presence of nasal defects (particularly involving the columella) distinguishes this condition from other syndromes, which was not shown in this clinical observation. Conclusion. We report the clinical case of an autosomal-dominant disease, Werner mesomelic dysplasia, which is a rare pathology with a typical clinical picture combined with congenital hip dislocation, which was not previously described. The molecular genetic examination confirms the presence of a pathogenic variant of the ZRS element of the SHH gene, which causes the development of Werner’s mesomelic dysplasia, but the mutation variant was not registered before, which requires an additional examination of the child’s relatives.

scholarly journals Tyrosinase gene mutations in the Chinese Han population with OCA1

2014 ◽  
Vol 96 ◽  
Author(s):  
NING LIU ◽  
XIANG DONG KONG ◽  
HUI RONG SHI ◽  
QING HUA WU ◽  
MIAO JIANG
Keyword(s):  
At Risk ◽  
Genetic Disorder ◽  
Severe Disease ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
Oculocutaneous Albinism ◽  
Compound Heterozygous ◽  
Chinese Han ◽  
Essential Information ◽  
Prenatal Genetic Diagnosis

SummaryOculocutaneous albinism (OCA) is a heterogeneous autosomal recessive genetic disorder that affects melanin synthesis. OCA results in reduced or absent pigmentation in the hair, skin and eyes. Type 1 OCA (OCA1) is the result of tyrosinase (TYR) gene mutations and is a severe disease type. This study investigated TYR mutations in a Chinese cohort with OCA1. This study included two parts: patient genetic study and prenatal genetic diagnosis. A total of 30 OCA1 patients were subjected to TYR gene mutation analysis. Ten pedigrees were included for prenatal genetic diagnosis. A total of 100 unrelated healthy Chinese individuals were genotyped for controls. The coding sequence and the intron/exon junctions of TYR were analysed by bidirectional DNA sequencing. In this study, 20 mutations were identified, four of which were novel. Of these 30 OCA1 patients, 25 patients were TYR compound heterozygous; two patients carried homozygous TYR mutations; and three were heterozygous. Among the ten prenatally genotyped fetuses, three fetuses carried compound heterozygous mutations and seven carried no mutation or only one mutant allele of TYR and appeared normal at birth. In conclusion, we identified four novel TYR mutations and showed that molecular-based prenatal screening to detect TYR mutations in a fetus at risk for OCA1 provided essential information for genetic counselling of couples at risk.

scholarly journals Joubert's syndrome as a cause of cholestasis in children

2020 ◽  
pp. 64-71
Author(s):  
V.S. Berezenko ◽  
◽  
H.Z. Mikhailyuk ◽  
Keyword(s):  
Molecular Genetic ◽  
Gene Mutations ◽  
Joubert Syndrome ◽  
Watch Glass ◽  
Cholestatic Liver Disease ◽  
Large Head ◽  
Palmar Erythema ◽  
Genetic Examination ◽  
Molecular Genetic Test ◽  
Chronic Intrahepatic Cholestasis

Literature review and a case report of Joubert syndrome in a preschool child are presented. This syndrome is accompanied by chronic intrahepatic cholestasis, characteristic facial dysmorphia, congenital malformations of the urinary system, eyes pathology, confirmed by a molecular genetic test of TMEM67 gene mutations. Diagnostic aspects of this pathology have been reviewed. The clinical case description. Boy K was admitted to the pediatric hepatology department with respiratory and renal failure, decompensated acidosis. On admission, complaints included shortness of breath, severe itching, pale and dry skin, poor appetite and delayed physical development. On examination, dysembryogenic stigmas: large head circumference, elongated face, protruding forehead, high rounded eyebrows, deeply set eyes, hypertelorism, antimongoloid incision of the eyes, low auricles. The skin was pale, dry with the scratch marks on the arms and legs flexor surfaces. Ankles, wrists skin lichenification, bruising and hyperpigmentation was observed. Moderate palmar erythema, spider veins on the abdomen, watch-glass nails were present. The abdomen was enlarged due to hepatosplenomegaly. A clinical and paraclinical examination was conducted, the patient was consulted by related specialists. Based on the obtained data and molecular genetic examination, the diagnosis was made. Conclusion. Joubert's syndrome may have a clinical presentation similar to that in cholestatic liver disease with typical clinical and laboratory symptoms. The molecular genetic testing is an important workup component in children with liver pathology combined with damage to other organs and systems. Successful treatment is possible providing a multidisciplinary approach used. The study was conducted by the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the abovementioned institution. Informed consent of the child's parents was obtained for the research. The authors declare no conflict of interest. Keywords: Joubert syndrome, cholestasis, children.

scholarly journals Analysis of beta globin gene mutations in Diyarbakir

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Selahaddin Tekeş ◽  
Diclehan Oral ◽  
Murat Söker ◽  
Selda Şimşek ◽  
Veysiye Hülya Uzel ◽  
...  
Keyword(s):  
Globin Gene ◽  
Molecular Genetic ◽  
Point Mutations ◽  
Gene Mutations ◽  
Turkish Population ◽  
University Hospital ◽  
Beta Thalassemia ◽  
Amplification Refractory Mutation System ◽  
Compound Heterozygous ◽  
Common Mutation

Abstract Objectives Hemoglobin disorders are quite heterogeneous in the Turkish population. Up to now, more than forty different beta thalassemia mutations and 60 hemoglobin variants have been characterized in the country. The aim of this study was to investigate genetic heterogeneity of HBB gene mutations in patients and their parents at Southeastern Anatolia in Turkey. Methods Genomic DNA was isolated from 145 thalassemic patients’ blood samples and their parents in this study. Ten different HBB gene mutations HBB:c.-80T>A, HBB:c.17_18delCT, HBB:c.25_26delAA, HBB:c.92+1G>A, HBB:c.92+5G>C, HBB:c.92+6T>C, HBB:c.93-21G>A, HBB:c.135delC, HBB:c.315+1G>A, HBB:c.316-106C>G were screened by amplification refractory mutation system. Four Hb variants and some rare beta thalassemia mutation were characterized by DNA sequencing. Results In this study, 97 homozygous and 48 compound heterozygous thalassemic patients were diagnosed by molecular genetic analyses. As a results, 18 β-thalassemia mutations and four abnormal hemoglobins; HBB:c.20A>T, HBB:c.364G>C, HBB:c.34G>A and HBB:c.208G>A were detected at Dicle University Hospital. Conclusions In the results, HBB:c.93-21G>A is the most common mutation in the region. Three mutations [(HBB:c.93-21G>A), (HBB:c.25_26delAA) and (HBB:c.135delC)] account for about 58 per cent of all the point mutations. Except HBB:c.20A>T and HBB:c.364G>C, two silent Hb variants (HBB:c.34G>A and HBB:c.208G>A) were detected in this study. Hb Hamilton [β11 (GTT>ATT) Val>Ile] was seen first time in Turkey.

Characterization of plasminogen variants in healthy subjects and plasminogen mutants in patients with inherited plasminogen deficiency by isoelectric focusing gel electrophoresis

2004 ◽  
Vol 92 (08) ◽  
pp. 352-357 ◽  
Author(s):  
Katrin Tefs ◽  
Maria Georgieva ◽  
Stefan Seregard ◽  
Campbell Tait ◽  
Lori Luchtman-Jones ◽  
...  
Keyword(s):  
Isoelectric Focusing ◽  
Gel Electrophoresis ◽  
Healthy Subjects ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Molecular Genetic Analysis ◽  
Compound Heterozygous ◽  
Wild Type ◽  
Ligneous Conjunctivitis

SummaryPlasmin(ogen) plays an important role in fibrinolysis and wound healing. Severe hypoplasminogenemia has recently been linked to ligneous conjunctivitis. Plasminogen (plg) is known as a polymorphic protein and most of these variants have been identified using isoelectric focusing (IEF) gel electrophoresis. Here, we studied common plg variants from healthy subjects and plg mutants from three patients with hypoplasminogenemia and three subjects with dysplasminogenemia by molecular genetic analysis and IEF. Analysis of 24 healthy subjects showed that subjects with the most common IEF plg phenotype A (n = 12) were homozygous for aspartate at position 453 (453D), while both subjects with IEF plg phenotype B were homozygous for asparagine at this position (453N). Subjects with IEF plg phenotype AB (n = 10) were compound-heterozygous for 453D/453N. Three patients with severe hypoplasminogenemia and different plg gene mutations exhibited characteristic “abnormal” IEF band patterns when compared with IEF plg phenotypes A and B. In all heterozygous family members the observed IEF plg phenotype was derived from the wild type plg molecule only, probably due to low concentration of the mutant plg molecule in plasma. In contrast, in three unrelated subjects with heterozygous dysplasminogenemia an equal “mixture” of wild type and mutant plg was found by IEF analysis. In conclusion, plg phenotyping by IEF in combination with molecular analysis of the plg gene seems to be a useful method for characterization of plg variants and mutants.

scholarly journals Neuroblastoma Amplified Sequence Gene Mutations Inducing Acute Kidney and Liver Injury in an Adolescent Female

2020 ◽  
Vol 10 (3) ◽  
pp. 117-123
Author(s):  
Roy Rafael Dayan ◽  
O.N. Ray Bignall II ◽  
Sheryl Johnson ◽  
Francisco Flores ◽  
Oded Volovelsky
Keyword(s):  
Liver Injury ◽  
Gene Mutation ◽  
Gene Mutations ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Compound Heterozygous ◽  
Adolescent Female ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Tubular Necrosis ◽  
Causative Relation

Acute liver injury (ALI) in children is a life-threatening event, and a definitive etiology can be identified in approximately 50% of cases. Neuroblastoma amplified sequence (NBAS) gene mutations have been associated with a broad phenotypic spectrum of this disease, ranging from recurrent episodes of fever-induced liver injuries to multiorgan involvement, including frequent infections as well as skeletal and immunological abnormalities. Here, we describe an adolescent female with a confirmed compound heterozygous NBAS gene mutation who presented with an episode of ALI complicated by severe acute kidney injury (AKI). The kidney injury was most probably driven by an intrinsic insult, as noted by elevated neutrophil gelatinase-associated lipocalin levels and a kidney biopsy demonstrating severe tubular damage consistent with acute tubular necrosis. While the patient’s liver function and mental status showed significant improvement with supportive care, recovery of kidney function was delayed, and the patient required acute hemodialysis. We suggest a causative relation between the NBAS gene mutation and severe AKI.

Novel DIO1 gene mutation acting as phenotype modifier for novel compound heterozygous TPO gene mutations causing congenital hypothyroidism

Thyroid ◽  
2021 ◽  
Author(s):  
Aryel E Furman ◽  
Zeina Hannoush ◽  
Francisco X Barrera Echegoyen ◽  
Alexandra M Dumitrescu ◽  
Samuel Refetoff ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Congenital Hypothyroidism ◽  
Gene Mutations ◽  
Compound Heterozygous

scholarly journals Modern opportunities and indications for genetic diagnosis of male infertility

2019 ◽  
pp. 3-15
Author(s):  
Т.М. Сорокина ◽  
О.А. Соловова ◽  
В.Б. Черных
Keyword(s):  
Male Infertility ◽  
Recurrent Miscarriage ◽  
Genetic Diagnosis ◽  
Disorders Of Sex Development ◽  
Gene Mutations ◽  
Genomic Analysis ◽  
Copy Number Variations ◽  
Genetic Causes ◽  
Sex Development ◽  
Genetic Examination

Тяжелые формы мужского и женского бесплодия, привычного невынашивания беременности, аномалий формирования пола часто обусловлены генетическими причинами или связаны с генетическими факторами. Медико-генетическое обследование и консультирование пациентов с нарушением репродукции зачастую ограничивается использованием стандартных рутинных исследований, поэтому не позволяет выявить многие наследственные формы репродуктивной патологии. Методы геномного анализа позволяют повысить эффективность диагностики генетически обусловленных нарушений репродукции, вызванных генными мутациями и вариациями числа копий (CNV), но их пока широко не используют в практическое медицине. В статье рассмотрены современные возможности медико-генетического обследования мужчин с нарушением фертильности, а также приведены показания и алгоритмы диагностики генетических причин мужского бесплодия, связанного с различными формами патозооспермии. Evere forms of male and female infertility, recurrent miscarriage, abnormalities in disorders of sex development are often due to genetic causes or are associated with genetic factors. Genetic examination and counseling of patients with reproductive problems is often limited to the use of standard routine techniques, therefore, it is not possible to identify many hereditary forms of reproductive pathology. Genomic analysis methods can improve the diagnosis of genetic reproductive disorders caused by gene mutations and copy number variations (CNVs), but they are not yet widely used in practical medicine. The article discusses the modern possibilities of medical-genetic examination of infertile men with, as well as the indications and diagnostic algorithms for the genetic causes of male infertility associated with various forms of pathozoospermia.

scholarly journals Genetic examination of children with hearing impairment in the astrakhan region

2020 ◽  
Vol 19 (5) ◽  
pp. 44-50
Author(s):  
E. A. Grigor’eva ◽  
◽  
E. A. Ivanova ◽  
T. G. Markova ◽  
S. S. Chibisova ◽  
...  
Keyword(s):  
Hearing Impairment ◽  
Russian Federation ◽  
Single Gene ◽  
Gene Mutations ◽  
Ethnic Composition ◽  
Gjb2 Gene ◽  
Compound Heterozygous ◽  
Recessive Mutations ◽  
Genetic Examination ◽  
The Russian Federation

To study the prevalence of mutations in the GJB2 gene in deaf and deaf children in the Astrakhan region and compare them with the frequency of mutations in children with hearing impairment living in other regions of the Russian Federation taking into account regional characteristics. This work describes the results of epidemiological, audiological analysis, medical and genetic examination of children. We examined 6 frequent recessive mutations in the GJB2 gene in a group of 79 hearing impaired children registered with the Regional Center for Hearing Rehabilitation. Mutations were detected in 36 children (46%), with two mutations found only in 18 children (23%), and another 18 children were carriers of the same mutation. In 9 children (11.5%), the 35 delG mutation was detected in the homozygous state and in 9 children (11.5%) in the compound heterozygous state with a different mutation. We have shown that the results obtained do not correspond to the high prevalence of gene mutations (more than 50%) in groups of children with hearing impairment, established in most regions of the Russian Federation, as well as in several countries in Europe, China and Japan. The large number of carriers of a single gene mutation indicates the need to study the entire gene sequence and may be a consequence of the mixed ethnic composition of the subjects.

scholarly journals Molecular Characterization and Frequencies of Different Genetic Ameliorating Factors in Transfusion Dependent Thalassemia Patients from District Peshawar

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4816-4816
Author(s):  
Gulrukh Mehmood ◽  
Abid Sohail Taj ◽  
Arshi Naz ◽  
Tariq Masood Khan
Keyword(s):  
Gene Mutation ◽  
Conflicts Of Interest ◽  
Globin Gene ◽  
Severe Disease ◽  
Genetic Modifier ◽  
Gene Mutations ◽  
Clinical Severity ◽  
Health Concern ◽  
Compound Heterozygous ◽  
Globin Genes

Background Thalassemia is one of the most common genetic blood disorders worldwide. The carrier rate of β thalassemia in Pakistan is found to be around 5-7%, rendering it a major health concern. Approximately 5000 children are diagnosed with thalassemia major every year in Pakistan due to consanguineous marriages. More than 200 causative molecular defects have been identified in β-globin genes. About 20 mutations account for 90% of the abnormal β-genes. Clinical severity of β-thalassemia is modified by different factors. The important ones include the type of disease causing mutation and the ability to produce α and γ globin chains. A better understanding of these ameliorating factors may have a significant impact on disease management. Objectives 1. To re-assess diagnoses among local multi-transfused thalassemia syndrome patients. 2. To determine frequency of various genetic determinants of milder phenotypes of thalassemia among study patients. Methods Transfusion dependent thalassemia patients, upto 15 years age, were enrolled from Fatimid Foundation, Peshawar Pakistan. A comprehensive questionnaire encompassing demographic and clinical data was filled out for each patient. Genetic analyses for 2 alpha (α) and 13 prevalent beta (β) gene mutations and for polymorphisms at Xmn1-HBG2 and BCL11A were carried out on blood samples of the patients at National Institute of Blood Diseases, Karachi Pakistan. The data collected was analysed at Khyber Medical University (KMU) Peshawar Pakistan. Results A total of 54 transfusion dependent thalassemia patients were enrolled into the study. Homozygous or compound heterozygous combinations of β-globin gene mutations were identified in all the study patients. Eleven patients were found to have a co-existing heterozygous α (3.7kb) deletion, two patients had Xmn1-HBG2 polymorphism and 38 had BCL11A polymorphism. Homozygous Fr 8-9 was the most frequent mutation, found in 19 (35.2%) patients. Only 13 patients were found to have isolated β-globin gene mutations. In total, 46 (85.2%) study patients were identified to have an ameliorating genetic factor (a co-existing α-globin gene mutation, an Xmn1-HBG2 polymorphism or a BCL11A polymorphism) besides the main β-globin gene mutation. Conclusion It was concluded that co-existing genetic ameliorating factors are frequently found in transfusion dependent β-thalassemia patients of Peshawar District. These factors impart a milder phenotype to an otherwise severe disease. It is hence suggested that β-thalassemia patients from District Peshawar be screened for these factors and due consideration be paid by the physician in devising management plans. Key Words Thalassemia, Genetic modifier in thalassemia, Transfusion dependent Anaemia, Xmn1 polymorphism Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document