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1.
Mol Ther ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31543414

RESUMO

Symptoms of spinal muscular atrophy (SMA) disease typically begin in the late prenatal or the early postnatal period of life. The intrauterine (IU) correction of gene expression, fetal gene therapy, could offer effective gene therapy approach for early onset diseases. Hence, the overall goal of this study was to investigate the efficacy of human survival motor neuron (hSMN) gene expression after IU delivery in SMA mouse embryos. First, we found that IU-intracerebroventricular (i.c.v.) injection of adeno-associated virus serotype-9 (AAV9)-EGFP led to extensive expression of EGFP protein in different parts of the CNS with a great number of transduced neural stem cells. Then, to implement the fetal gene therapy, mouse fetuses received a single i.c.v. injection of a single-stranded (ss) or self-complementary (sc) AAV9-SMN vector that led to a lifespan of 93 (median of 63) or 171 (median 105) days for SMA mice. The muscle pathology and number of the motor neurons also improved in both study groups, with slightly better results coming from scAAV treatment. Consequently, fetal gene therapy may provide an alternative therapeutic approach for treating inherited diseases such as SMA that lead to prenatal death or lifelong irreversible damage.

2.
Turk J Gastroenterol ; 30(9): 789-800, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31530523

RESUMO

BACKGROUND/AIMS: The aim of the present study was to demonstrate the histopathological findings in gastrointestinal (GI) biopsies in adults with common variable immunodeficiency (CVID). MATERIALS AND METHODS: A total of 172 GI biopsies of 26 patients with CVID obtained over a 16-year period were reevaluated. Findings were analyzed using descriptive analyzes and χ2 test. RESULTS: Female-to-male ratio was 1.36. The median age at diagnosis was 36±13.94 (16-72) years. Chronic esophagitis was noted in 3 patients. The absence of plasma cells in the stomach, duodenum, and colon was observed in 16, 14, and 9 patients, respectively. Divergent results for the presence of plasma cells in concurrent stomach and duodenum samples were found in 11 (44%) patients. Nodular lymphoid hyperplasia (NLH) was notable in the duodenum (56%). The mean number of eosinophils in one high-power field was significantly higher in duodenal biopsies with NLH (27.21 vs. 14.37, p=0.002). Active inflammation was more prominent in the colon (91%) than in the stomach (65%) and duodenum (60%). Helicobacter pylori infection was found in 57.6%, including a case with persistent infection by the coccoid form. Celiac-like villous blunting and increased intraepithelial lymphocytes were seen in 40% and 24%, respectively. In addition, 23% had giardiasis associated with acute duodenitis and duodenal NLH (p<0.05). CONCLUSION: CVID gastroenteropathy is a challenging entity, and due to the heterogeneity in the presence and distribution of plasma cells throughout the GI tract and diverse disease course, multiple concurrent biopsies may be needed for tissue diagnosis. Duodenal CVID may present with villous alterations and giardiasis, and NLH appears to be an important clue in the duodenum. The association between duodenal NLH and eosinophil infiltration deserves further investigation.

3.
Eur J Med Genet ; 62(10): 103725, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31319225

RESUMO

Next generation sequencing has provided great advancements in genetic diagnosis of Mendalian disorders. Simultaneous sequencing of many genes has become increasingly cheaper and faster. Recently, a number of gene panels have been established for the diagnosis of specific disease groups. The aim of this study is to evaluate the utility of an inherited disease panel in pediatric onset Mendelian diseases. Two hundred and seventeen probands and 10 carriers molecularly analyzed using a TruSight Inherited Disease® Panel which included 552 genes responsible for pediatric onset Mendelian disorders, were enrolled in the study. The clinical phenotype, sequencing data, pretest and posttest diagnoses were evaluated. The patients in the study were classified into two groups. Group 1 (n:209) included the patients having a clinical diagnosis prior to molecular analysis. Group 2 (n:18) included the patients undiagnosed clinically prior to molecular analysis. Targeted panel provided a molecular diagnosis in 37% (84 of 227 cases) of all cases. The molecular diagnostic rate was 40.2% in patients with a specific prior clinical diagnosis. However, in patients having no primary clinical diagnosis no pathogenic variants were found. In 14 patients, a molecular diagnosis differing from the established clinical diagnosis was made. In conclusion, a targeted panel covering a high number of genes responsible for broad phenotypic spectrum can provide improved levels of diagnosis in patients with pediatric onset Mendelian diseases. A careful clinical evaluation of patients prior to the application of a next generation sequencing method leads to the best alternative approach for a conclusive molecular diagnosis.

4.
Pediatr Blood Cancer ; 66(10): e27923, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31321910

RESUMO

BACKGROUND: Severe congenital neutropenia is a rare disease, and autosomal dominantly inherited ELANE mutation is the most frequently observed genetic defect in the registries from North America and Western Europe. However, in eastern countries where consanguineous marriages are common, autosomal recessive forms might be more frequent. METHOD: Two hundred and sixteen patients with severe congenital neutropenia from 28 different pediatric centers in Turkey were registered. RESULTS: The most frequently observed mutation was HAX1 mutation (n = 78, 36.1%). A heterozygous ELANE mutation was detected in 29 patients (13.4%) in our cohort. Biallelic mutations of G6PC3 (n = 9, 4.3%), CSF3R (n = 6, 2.9%), and JAGN1 (n = 2, 1%) were also observed. Granulocyte colony-stimulating factor treatment was given to 174 patients (80.6%). Two patients died with infectious complications, and five patients developed myelodysplastic syndrome/acute myeloblastic leukemia. The mean (± mean standard error) follow-up period was 129.7 ± 76.3 months, and overall survival was 96.8% (CI, 94.4-99.1%) at the age of 15 years. In Turkey, severe congenital neutropenia mostly resulted from the p W44X mutation in the HAX1 gene. CONCLUSION: In Turkey, mutation analysis should be started with HAX1, and if this is negative, ELANE and G6PC3 should be checked. Because of the very high percentage of consanguineous marriage, rare mutations should be tested in patients with a negative mutation screen.

5.
Eur J Ophthalmol ; : 1120672119858225, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31232112

RESUMO

PURPOSE: To investigate vitamin D receptor polymorphisms in ocular surface squamous cell neoplasm and to evaluate the relationship between the identified polymorphisms and susceptibility to ocular surface squamous cell neoplasm and the clinical course. MATERIALS AND METHODS: A totala of 70 patients with ocular surface squamous cell neoplasm (study group) and 75 healthy age and gender-matched individuals (control group) were included in the study. Vitamin D receptor FokI and BsmI polymorphisms were examined. The relationships between histopathological diagnosis, recurrence rates, tumor stage, and identified polymorphisms were investigated. RESULTS: Histopathologically, 43 of the cases were squamous cell carcinoma and 27 of the cases were conjunctival intraepithelial neoplasia. The frequency of FokI (FF, Ff, ff) and BsmI (BB, Bb, bb) polymorphism genotype of vitamin D receptor gene were similar in the groups. The frequency of polymorphism (heterozygous or homozygous) for BsmI (Bb and bb) was significantly higher (p = 0.046) in the study group, while no difference was found between the groups in terms of polymorphic carriers (heterozygous or homozygous) for FokI. There was no correlation between tumor stage, recurrence-polymorphism frequency, and patient age-polymorphism frequency. CONCLUSION: It is known that active vitamin D inhibits the growth of cancer cells by binding to vitamin D receptor with regulation of genes responsible for cell proliferation. The presence of BsmI polymorphism in vitamin D receptor, in particular bb genotype and b allele, appears to be associated with the susceptibility of ocular surface squamous cell neoplasm. BsmI gene polymorphisms of vitamin D receptor might play an effective role in the formation, progression, and in the course of ocular surface squamous cell neoplasm.

6.
Gene ; 707: 212-215, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31102717

RESUMO

BACKGROUND: Alzheimer's disease is a progressive, irreversible neurodegenerative disorder characterized by loss of memory and cognitive skills. More than 90% of cases are sporadic and have later age of onset. Many studies have shown a genetic predisposition for late onset Alzheimer's disease (LOAD). The most studied genetic predisposition factor is apolipoprotein E gene besides other susceptibility genes involved in vascular pathologies, homocysteine metabolism, and neuronal growth and differentiation such as methylenetetrahydrofolate reductase (MTHFR), angiotensin-converting enzyme (ACE), APOB and brain derived neurotrophic factor (BDNF). METHODS: In this study Factor V Leiden (G1691A) and H1299R, prothrombin G20210A, Factor XIII V34L, B-fibrinogen -455G>A, PAI-1 5G/4G, HPA1 b/a, MTHFR C677T, MTHFR A1298C, APOE, ACE I/D, BDNF C270T and G196A polymorphisms were evaluated in 100 LOAD patients and 100 age matched healthy controls. RESULTS: APOE4 allele, MTHFR CCA1298C and BDNF TTC270T genotypes were significantly higher in LOAD patients compared to the control group (p < 0.001, p = 0.04, p = 0.03, respectively). There were no significant associations between other genotypes and allele frequencies. Mini-Mental State Examination (MMSE) scores and age at onset of the patients were also evaluated for each and combined genotypes. Age at onset was significantly lowered by about approximately 4 and 5 years in patients carrying BDNF TTC270T and MTHFR TTC677T genotypes, respectively. CONCLUSION: APOE, MTHFR A1298C and BDNF C270T polymorphisms may be associated with LOAD and BDNF and MTHFR alleles may play a role in the age at onset of the LOAD.


Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
7.
Artigo em Inglês | MEDLINE | ID: mdl-31088041

RESUMO

Neurofibromatosis Noonan Syndrome (NFNS) is a rare RASopathy syndrome, resulted from NF1 gene mutations. NFNS is characterized by phenotypic features of both Neurofibromatosis type 1 (NF1) and Noonan syndrome. Plexiform neurofibromas are an unusual finding of NFNS. A 7 year-old girl with typical clinical features of NF1 was referred to our clinic due to short stature and abnormal genital appearance. Regarding dysmorphic features a clinical diagnosis of NFNS was considered in the patient, and following molecular analysis revealed a novel heterozygous c.3052_3056delTTAGT (p.L1018X) variant in NF1 gene. Although evaluation for genital virilization including karyotype and hormonal studies were resulted normal, imaging studies revealed a diffuse genital plexiform neurofibroma. Although plexiform neurofibromas are seen rarely, should be considered in the differential diagnosis of genital virilization in NFNS patients to prevent unnecessary laboratory tests.

8.
Artigo em Inglês | MEDLINE | ID: mdl-30968679

RESUMO

Aromatase deficiency rarely causes a 46, XX sexual differentiation disorder. The CYP19A1 gene encodes the aromatase enzyme which catalyses the conversion of androgens to oestrogens. In cases with 46, XX karyotype, mutations in the CYP19A1 gene can lead to disorders of sex development. Clinical findings in aromatase deficiency vary depending on the degree of deficiency. Due to the effect of increased androgens; acne, cliteromegaly and hirsutism can be observed in mothers with placental aromatase deficiency. A decrease in the maternal virilisation symptoms is observable in the postpartum period. It is rarely reported that there is no virilization in pregnancy. In this study, two 46, XX sibling having the p.R115X (c.343 C>T) novel pathogenic variant in the CYP19A1 gene and raised as different genders and no maternal virilisation in pregnancy are presented. In conclusion, 46, XX virilised females should be examined in terms of aromatase deficiency once congenital adrenal hyperplasia has been excluded, even if no history of maternal virilisation during pregnancy is present.

9.
Artigo em Inglês | MEDLINE | ID: mdl-30499904

RESUMO

Severe Congenital Neutropenia (SCN) is a rare inherited disease characterized by an absolute neutrophil count (ANC) lower than 500/µL. Genetic heterogeneity and biallelic CSF3R mutation has rarely been identified as an underlying genetic defect in SCN. The majority of SCN patients respond to granulocyte colony stimulating factor treatment; however, in patients with inherited CSF3R mutation, ANC cannot generally be increased with granulocyte colony stimulating factor treatment. In such cases, granulocyte macrophage colony stimulating factor presents as an effective treatment option. Herein, we report a case of a 5-year-old SCN girl with homozygous c610-611 del ins AG (p.Q204R) mutation in the CSF3R gene, who was successfully treated with granulocyte macrophage colony stimulating factor.

10.
Blood Cells Mol Dis ; 2018 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-30473482

RESUMO

Gaucher Disease (GD) is the most common lysosomal storage disorder has traditionally been classified into three clinical phenotypes. Type 3 GD is characterized by neurological involvement but neurological symptoms generally appear later in life than in type 2 disease. Neutropenia is much rarer than other hematological manifestations in GD and has not been scrutinized adequately. Severe congenital neutropenia (SCN) is a rare disease entity which is characterized by a paucity of peripherally circulating neutrophils with arrest of neutrophil maturation at the promyelocyte stage and consequent increased susceptibility to severe and recurrent infections. We report a patient who presented in the first year of life with visceral involvement and severe neutropenia in whom the propositus had a unique coexistence of Gaucher Disease and severe congenital neutropenia associated with a mutation in HAX1. In contrast to his expired siblings he had experienced no severe infections. These clinical observations suggest that enzyme replacement therapy may display a modulating factor with respect to the clinical course of SCN. SYNOPSIS: Our patient is the only report of the combination of Gaucher Disease and Kostmann Syndrome in the literature. The clinical course of our patient is not severe when comparing with exitus siblings and other Kostmann Syndrome patients. But when considering the patient's only clinical difference is ERT, this case is very important to emphasise the role of enzyme replacement therapy in bone marrow.

11.
Int Arch Allergy Immunol ; : 1-10, 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30278448

RESUMO

BACKGROUND: How genotype affects phenotype in hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) has not been totally clarified. In this study, we investigated the relationship between different types of mutations and various phenotypic characteristics. METHODS: Clinical data from 81 patients from 47 families were recorded. Complement proteins were analyzed from 61 untreated patients. The coding exons and the exon-intron boundaries of the SERPING1 gene were sequenced, and deletion/duplication analysis with multiple ligation dependent probe amplification was performed. The relationship of complement protein with the mutation type was analyzed by using generalized estimating equations. RESULTS: Thirty-five different mutations (15 novel and 2/15 homozygous) were identified. There was no causative mutation in 6 patients (7.4%). Patients with deletion and large deletion had the lowest (5.05%, 0-18.7; 5.8%, 0-16.5%, respectively), and the none mutation group had the highest C1 inhibitor function (23.3%, 11-78%, p < 0.001). C1 inhibitor function levels decreased as the age of the disease progressed (r = -0.352, p = 0.005). Lower C1 inhibitor function levels caused severer disease (r = -0.404, p = 0.001) and more frequent annual attacks (r = -0.289, p = 0.024). In the off-attack period, C1q levels were lower than normal in 9.8% of the patients. CONCLUSION: Deletion mutations may represent the most unfavorable effect on C1 inhibitor function. The earlier disease onset age could be a sign for lower C1 inhibitor function levels in adult life. C1q levels could also be low in C1-INH-HAE patients, as in acquired angioedema. Lower C1 inhibitor function can predict disease severity and may have negative impacts on the course of C1-INH-HAE.

12.
J Pediatr Endocrinol Metab ; 31(11): 1289-1293, 2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30307897

RESUMO

Background Familial apo C-II deficiency is a rare hereditary disorder frequently caused by lipoprotein lipase (LPL) and APOC2 gene mutations. To date, less than 30 patients with familial apo C-II deficiency with 24 different mutations have been identified in the literature. Here, we describe two familial chylomicronemia syndrome cases in infants with two novel mutations of the APOC2 gene. Case presentation Case 1, a 46-day-old female, was admitted to our hospital for evaluation due to the lipemic appearance of the blood sample. A clinical examination revealed hepatomegaly and lipemia retinalis. Triglyceride level of 6295 mg/dL was decreased with a strict low-fat diet, medium-chain triglycerides (MCT) oil-rich formula and omega-3 fatty acid supplementation. Due to low adherence to the diet, TG elevation was detected and fresh frozen plasma (10 mL/kg/day) was administered for 2 days. A novel homozygous p.Q25X (c.73C>T) mutation in the APOC2 gene was detected. Case 2, a 10-month-old female patient, referred to our center for the differential diagnosis of hyperlipidemia as her blood sample could not be assessed due to its lipemic appearance. Laboratory examinations showed a TG level of 4520 mg/dL which was reduced with a low-fat diet, MCT oil-rich formula and omega-3 fatty acid supplementation. Hepatosteatosis and splenomegaly were determined using abdominal sonography. A novel homozygous IVS2+6T>G (c.55+6T>G) mutation in the APOC2 gene was identified. Conclusions We describe two novel homozygous mutations (p.Q25X [c.73C>T] and IVS2+6T>G [c.55+6T>G]) in the APOC2 gene in infants with hyperchylomicronemia. To the best of our knowledge, Case 1 is the youngest patient with familial apo C-II deficiency in the literature to date.

13.
Psychol Med ; : 1-11, 2018 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-30101737

RESUMO

BACKGROUND: Psychotic experiences (PEs) may predict a range of common, non-psychotic disorders as well as psychotic disorders. In this representative, general population-based cohort study, both psychotic and non-psychotic disorder outcomes of PE were analysed, as were potential moderators. METHODS: Addresses were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighbourhoods at baseline (n = 4011). Participants were interviewed with the Composite International Diagnostic Interview (CIDI) both at baseline and at 6-year follow-up. Participants with PE at baseline were clinically re-interviewed with the SCID-I at follow-up. The role of socio-demographics, characteristics of PE, co-occurrence of mood disorders and family history of mental disorders were tested in the association between baseline PE and follow-up diagnosis. RESULTS: In the participants with baseline PE, the psychotic disorder diagnosis rate at follow up was 7.0% - much lower than the rates of DSM-IV mood disorders without psychotic features (42.8%) and other non-psychotic disorders (24.1%). Within the group with baseline PE, female sex, lower socio-economic status, co-occurrence of mood disorders, family history of a mental disorder and persistence of PE predicted any follow-up DSM diagnosis. Furthermore, onset of psychotic v. non-psychotic disorder was predicted by younger age (15-30 years), co-presence of delusional and hallucinatory PE and family history of severe mental illness. CONCLUSION: The outcome of PE appears to be a consequence of baseline severity of multidimensional psychopathology and familial risk. It may be useful to consider PE as a risk indicator that has trans-diagnostic value.

14.
Artigo em Inglês | MEDLINE | ID: mdl-30028820

RESUMO

Congenital neutropenia (CN) is a rare disorder, and the most common gene responsible for CN is ELANE. Furthermore, the mutations of HAX1, G6PC3, and JAGN1 genes may cause CN. These patients generally find great benefit from subcutaneous administration of Granulocyte Colony Stimulating Factor (GCSF). In recent years, Biallelic Colony Stimulating Factor 3 Receptor (CSF3R) mutations have been described as an underlying defect of CN in several children. In contrast to the previous group, the patients who have a CSF3R mutation do not respond to GCSF treatment. Here, we present a CN patient with hypomorphic biallelic CSF3R mutation responding to GCSF.

15.
J Pediatr Endocrinol Metab ; 31(8): 917-926, 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-29995633

RESUMO

Background Biotinidase deficiency (BD) is an autosomal recessively inherited disorder of biotin recycling. It is classified into two levels based on the biotinidase enzyme activity: partial deficiency (10%-30% enzyme activity) and profound deficiency (0%-10% enzyme activity). The aims of this study were to evaluate our patients with BD, identify the spectrum of biotinidase (BTD) gene mutations in Turkish patients and to determine the clinical and laboratory findings of our patients and their follow-up period. Methods A total of 259 patients who were diagnosed with BD were enrolled in the study. One hundred and forty-eight patients were male (57.1%), and 111 patients were female (42.9%). Results The number of patients detected by newborn screening was 221 (85.3%). By family screening, 31 (12%) patients were diagnosed with BD. Seven patients (2.7%) had different initial complaints and were diagnosed with BD. Partial BD was detected in 186 (71.8%) patients, and the profound deficiency was detected in 73 (28.2%) patients. Most of our patients were asymptomatic. The most commonly found variants were p.D444H, p.R157H, c.98_104delinsTCC. The novel mutations which were detected in this study are p.D401N(c.1201G>A), p.A82G (c.245C>G), p.F128S(c.383T>C), c617_619del/TTG (p.Val207del), p.A287T(c.859G>A), p.S491H(c.1471A>G). The most common mutation was p.R157H in profound BD and p.D444H in partial BD. All diagnosed patients were treated with biotin. Conclusions The diagnosis of BD should be based on plasma biotinidase activity and molecular analysis. We determined the clinical and genetic spectra of a large group of patients with BD from Western Turkey. The frequent mutations in our study were similar to the literature. In this study, six novel mutations were described.


Assuntos
Deficiência de Biotinidase/epidemiologia , Deficiência de Biotinidase/genética , Biotinidase/genética , Mutação , Triagem Neonatal/métodos , Adolescente , Adulto , Deficiência de Biotinidase/diagnóstico , Criança , Pré-Escolar , Família , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Turquia/epidemiologia , Adulto Jovem
16.
Turk J Haematol ; 35(4): 229-259, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30040071

RESUMO

Objective: To examine granulocytic and non-granulocytic cells in children with severe congenital neutropenia (SCN) and their non-neutropenic parents. Materials and Methods: Fifteen patients with SCN and 21 non-neutropenic parents were evaluated for a) CD95, CD95 ligand, annexin V, propidium iodide, cell cycle, and lymphocyte subsets by flow cytometry; b) rapid cell senescence (of leukocytes) by senescence-associated ß-galactosidase stain; c) aggregation tests by aggregometer; d) in vitro bleeding time by PFA-100 instrument; e) mepacrine-labeled dense granule number of thrombocytes by fluorescence microscope; and f) hematomorphology by light and electron microscope. HAX1, ELANE, G6PC3, CSF3R, and JAGN1 mutations associated with SCN were studied in patients and several parents. Results: Significant increase in apoptosis and secondary necrosis in monocytes, lymphocytes, and granulocytes of the patients and parents was detected, irrespective of the mutation type. CD95 and CD95 ligand results implied that apoptosis was non-CD95-mediated. Leukocytes of 25%, 12.5%, and 0% of patients, parents, and controls showed rapid cell senescence. The cell cycle analysis testable in four cases showed G1 arrest and apoptosis in lymphocytes of three. The patients had HAX1 (n=6), ELANE (n=2), G6PC3 (n=2), and unidentified (n=5) mutations. The CD3, CD4, and NK lymphocytes were below normal levels in 16.6%, 8.3%, and 36.4% of the patients and in 0%, 0%, and 15.4% of the parents (controls: 0%, 0%, 5.6%). The thrombocytes aggregated at low rates, dense granule number/thrombocyte ratio was low, and in vitro bleeding time was prolonged in 37.5%-66.6% of patients and 33.3%-63.2% of parents (vs. 0% in controls). Under electron and/or light microscope, the neutrophils, monocytes, lymphocytes, and thrombocytes in the peripheral blood of both patients and parents were dysplastic and the bone marrow of patients revealed increased phagocytic activity, dysmegakaryopoiesis, and necrotic and apoptotic cells. Ultrastructurally, thrombocyte adhesion, aggregation, and release were inadequate. Conclusion: In cases of SCN, patients' pluripotent hematopoietic stem cells and their non-neutropenic parents are both affected irrespective of the genetic defect.

17.
Clin Neurol Neurosurg ; 172: 20-23, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29960101

RESUMO

L1 syndrome is a rare X linked recessive disorder caused bygene mutations in the L1 cell adhesion molecule (L1CAM), and characterized by hydrocephalus, intellectual disability, adducted thumbs and spasticity of the legs. The gene encodes a protein which plays an important role in neuronal development. Two unrelated L1 syndrome cases, with global developmental delay and hydrocephalus, were referred to pediatric genetics subdivision for genetic counseling. Bilateral adducted thumbs and spasticity in the lower extremities were also observed in both patients. Molecular analysis revealed two novel hemizygous mutations in the patients: a deletion mutation (c.749delG; p.Ser250Thrfs*51) and a splicing mutation (c.3166+1G>A). To conclude; in male patients with intellectual disability and hydrocephalus, where adducted thumbs are present, L1 syndrome should be considered.

18.
Pak J Med Sci ; 34(2): 463-467, 2018 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29805427

RESUMO

Objective: To investigate TGFB1 and LAMA1 gene polymorphisms in children with high myopia in order to determine the genetic basis of large myopic shifts causing severe visual impairment and complications. Methods: Seventy-four children with high myopia (≥6 diopters [D]; study group) and 77 emmetropic children (±0.5D; control group) were included. Genetic and polymorphism analyses were performed in the Medical Genetics Laboratory using DNA purified from the patients' blood samples. Results: Mean ages of the patients were 7.1±3 (3-13) and 9.6±1.8 (6-13) years in the study and control groups, respectively. Mean refraction in the high myopia group were -10.1±4.3D in the right and -8.9±3.6D in the left eye. LAMA1 gene analysis of the study group revealed heterozygous mutations in 34 patients (45.9%), homozygous mutations in 25 patients (33.8%), and no mutations in the remaining 15 patients (20.3%). In the control group, there were 31 subjects (40.3%) with heterozygous, 27 (35.1%) with homozygous LAMA1 mutations, and no mutations in 19 (24.7%) (p=0.73). TGFB1 gene analysis showed heterozygous mutations in 32 (43.2%) and homozygous mutations in 10 patients (13.5%) in the study group, while 32 patients (43.2%) had no mutations. In the control group, 35 subjects (45.5%) had heterozygous, 8 (10.4%) had homozygous, and 34 (44.1%) had no TGFB1 mutations (p=0.36). Conclusion: This is the first study to simultaneously examine two genes in high myopia in a Turkish population. However, we observed no significant differences in TGFB1 and LAMA1 gene polymorphisms in patients with high myopia compared to healthy subjects.

19.
Artigo em Inglês | MEDLINE | ID: mdl-29785763

RESUMO

There is little research on genetic risk for the extended psychosis phenotype ranging from psychotic experiences (PEs) to psychotic disorders (PDs). In this general population-based prospective cohort study, the longitudinal associations between BDNF-Val66Met polymorphism and the different levels of the extended psychosis phenotype were investigated. Addresses were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighborhoods at baseline (n = 4011). A nested case-control study (n = 366) recruited individuals with PEs and PDs as well as individuals with no psychotic symptoms. In this subgroup, blood sampling for genetic analysis and assessment of environmental exposures were carried out, followed by clinical re-appraisal at follow-up 6 years later (n = 254). The BDNF-Val66Met polymorphism was significantly associated with the extended psychosis phenotype. The pattern of the association was that the BDNF-Val66Met polymorphism impacted in a dose-response but extra-linear fashion, with stronger impact at the PD end of the extended psychosis phenotype. Associations were still significant after adjusting for sociodemographic factors and environmental exposures including life events, childhood adversity, socioeconomic status, urbanicity, and cannabis use. The BDNF-Val66Met polymorphism may index susceptibility to expression of psychosis along a spectrum.

20.
Endocr Res ; 43(4): 258-263, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29733702

RESUMO

PURPOSE: To describe an interesting subtype of familial partial lipodystrophy (FPLD). METHODS: The phenotype of this distinctive FPLD subtype was studied in three Turkish female siblings. RESULTS: Mutation testing was negative for the genes associated with lipodystrophy syndromes. In MRI studies, fat loss was prominent in the posterior aspects of the proximal lower limbs, whilst some fat was preserved in the anterior, medial and lateral aspects. Remarkably, fat tissue was preserved in the distal part of the limbs. Local fat accumulation was observed in the mons pubis area. Asymmetrical fat loss was also remarkable in the upper extremities. All three patients had severe insulin resistance associated with diabetes mellitus, acanthosis nigricans, hypertriglyceridemia and hepatic steatosis. Abnormal amounts of proteinuria were detected in all three subjects. Renal biopsy showed mild tubular atrophy, interstitial fibrosis, irregular thickening and wrinkling of glomerular basal membranes, small areas of segmental sclerosis and pedicel effacement. CONCLUSIONS: We reported a form of FPLD characterized by a striking pattern of highly selective partial fat loss and proteinuria.

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