Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 116
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Eur J Haematol ; 113(1): 82-89, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38556258

RESUMEN

OBJECTIVES: In congenital hemolytic anemias (CHA), it is not always possible to determine the specific diagnosis by evaluating clinical findings and conventional laboratory tests. The aim of this study is to evaluate the utility of next-generation sequencing (NGS) and clinical-exome-based copy number variant (CNV) analysis in patients with CHA. METHODS: One hundred and forty-three CHA cases from 115 unrelated families referred for molecular analysis were enrolled in the study. Molecular analysis was performed using two different clinical exome panels in 130 patients, and whole-exome sequencing in nine patients. Exome-based CNV calling was incorporated into the traditional single-nucleotide variant and small insertion/deletion analysis pipeline for NGS data in 92 cases. In four patients from the same family, the PK Gypsy variant was investigated using long-range polymerase chain reaction. RESULTS: Molecular diagnosis was established in 86% of the study group. The most frequently mutated genes were SPTB (31.7%) and PKLR (28.5%). CNV analysis of 92 cases revealed that three patients had different sizes of large deletions in the SPTB and six patients had a deletion in the PKLR. CONCLUSIONS: In this study, NGS provided a high molecular diagnostic rate in cases with rare CHA. Analysis of the CNVs contributed to the diagnostic success.


Asunto(s)
Anemia Hemolítica Congénita , Variaciones en el Número de Copia de ADN , Secuenciación del Exoma , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Humanos , Masculino , Femenino , Anemia Hemolítica Congénita/genética , Anemia Hemolítica Congénita/diagnóstico , Exoma , Niño , Preescolar , Lactante , Predisposición Genética a la Enfermedad , Adulto , Adolescente , Estudios de Asociación Genética , Adulto Joven
2.
Turk J Med Sci ; 52(3): 649-657, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36326316

RESUMEN

BACKGROUND: In tuberculsosis (TB), miRNA has been used as a biomarker to distinguish between healthy individuals and TB patients. The aim of this study was to investigate (i) the association of the miRNA and cytokine expression levels, the course of tuberculosis infection, clinical forms and response to treatment, and (ii) the effects of genotypic features of bacteria on the course of tuberculosis and the relationship between miRNA and cytokine expressions and bacterial genotypes. METHODS: A total of 200 cases (100: culture positive active tuberculosis, 50: quantiferon positive latent tuberculosis infection and 50: quantiferon negative healthy controls) were included in the study. For the tuberculosis group at the time of admission and after treatment, for the latent tuberculosis infection and healthy control groups at the time of admission, miRNA and cytokine expressions were determined. Genotyping of M.tuberculosis isolates was performed by spoligotyping method. RESULTS: While, in the comparison of miRNA expressions between the pretreatment patient group and the healthy control group, there was a statistically significant decrease in the expression of miR-454-3p, miR-15a-5p, miR-590-5p, miR-381, and miR-449a in the Pulmonary TB group, there was no significant change in miRNA expression in extrapulmonary TB patients. When the cytokine expressions of the patient group and the healthy control group were compared before treatment, the expressions of all cytokines in the patient group decreased. However, the only cytokine that showed a significantly lower expression was IL12A in PTB patients. DISCUSSION: There is no significant relationship between the clinical course of the disease, cytokine and miRNA expression, and the genotype of the bacteria.


Asunto(s)
Tuberculosis Latente , MicroARNs , Mycobacterium tuberculosis , Tuberculosis , Humanos , Tuberculosis Latente/genética , MicroARNs/genética , MicroARNs/metabolismo , Citocinas , Tuberculosis/genética , Mycobacterium tuberculosis/genética
3.
J Neurogenet ; 35(1): 23-28, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33216650

RESUMEN

To date, less than 10 pedigrees have been reported with ZNF335 mutations since it was discovered in 2012 and little is known about ZNF335-related clinical spectrum. We describe a 12 years old male patient who is only child of nonconsanguineous Turkish parents. Trio whole genome sequencing identified previously unreported compound heterozygous variants in ZNF335, namely, c.3889T > A p.(Ser1297Thr) and c.758G > A p.(Arg253Gln) where transmitted by his father and mother, respectively. Patient' magnetic resonance imaging findings were overlapping to those observed in the previous cases with ZNF335 mutations. Here we report the oldest patient with biallelic ZNF335 mutations. We recommend screening for ZNF335 defects in patients with basal ganglia anomaly, secondary white matter abnormalities and microcephaly.


Asunto(s)
Ganglios Basales/patología , Cerebelo/patología , Proteínas de Unión al ADN/genética , Mutación , Factores de Transcripción/genética , Atrofia/diagnóstico por imagen , Atrofia/genética , Atrofia/patología , Ganglios Basales/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Niño , Humanos , Imagen por Resonancia Magnética , Masculino , Linaje
4.
Am J Med Genet A ; 185(2): 461-468, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33258289

RESUMEN

3M syndrome is a rare autosomal recessive genetic disorder characterized by severe growth retardation, dysmorphic facial features, skeletal dysplasia, and normal intelligence. Variants in CUL7, OBSL1, and CCDC8 genes have been reported to be responsible for this syndrome. In this study, the clinical and molecular findings of four 3M syndrome cases from three families are presented. All cases had growth retardation, relative macrocephaly, and typical dysmorphic facial features. Their neurological developments were normal. Sequencing of CUL7, OBSL1, and CCDC8 genes revealed two different novel homozygous variants in CUL7 in Families 1 and 3 and a previously reported homozygous pathogenic variant in OBSL1 in Family 2. In conclusion, a comprehensive dysmorphological evaluation should be obtained in individuals presenting with short stature and in such individuals with typical facial and skeletal findings, 3M syndrome should be considered. Our report expands the genotype of 3M syndrome and emphasizes the importance of thorough physical and dysmorphological examination.


Asunto(s)
Proteínas Portadoras/genética , Proteínas Cullin/genética , Proteínas del Citoesqueleto/genética , Enanismo/genética , Hipotonía Muscular/genética , Columna Vertebral/anomalías , Adolescente , Niño , Preescolar , Enanismo/diagnóstico por imagen , Enanismo/patología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Homocigoto , Humanos , Lactante , Masculino , Hipotonía Muscular/diagnóstico por imagen , Hipotonía Muscular/patología , Mutación , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/patología
5.
Pediatr Res ; 90(3): 559-564, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33096541

RESUMEN

BACKGROUND: Apoptosis that occurs after hypoxia/reoxygenation (H/R) has an important role in the pathogenesis of necrotizing enterocolitis (NEC). Telomerase activity, showing the regeneration capacity, may also be important in the recovery process. Therefore, we aimed to investigate the effects of insulin-like growth factor-1 (IGF-1) and erythropoietin (EPO) on apoptosis and telomerase activity in an H/R model. METHODS: Young mice were divided into four groups each containing ten Balb/c mice. Group 1 (H/R) were exposed to H/R; group 2 and group 3 were pretreated with IGF-1 and EPO, respectively, for 7 days before H/R. Group 4 served as control. Intestinal injury was evaluated by histological scoring and assessment of apoptosis was performed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) test. Proapoptotic and antiapoptotic gene expressions and telomerase activity were analyzed by real-time PCR. RESULTS: IGF-1- and EPO-treated animals had decreased histological damage and apoptosis, confirmed by TUNEL test and caspase activity. Telomerase activity was increased in these animals in addition to increased expression of antiapoptotic genes. However, proapoptotic gene expressions were not statistically different. CONCLUSIONS: The protective effects of IGF-1 and EPO in H/R damage may be through increased expression of antiapoptotic genes and increased telomerase activity, especially for IGF-1. IMPACT: This is a comprehensive study measuring various variables, namely IGF-1, EPO, apoptosis, apoptotic and antiapoptotic genes, and telomerase activity in the NEC model. The intestinal protective effects of IGF-1 and EPO in H/R damage may occur through increased expression of antiapoptotic genes and increased telomerase activity. To the best of our knowledge, telomerase activity has not been investigated in the NEC model before. Regarding our results, novel strategies may be implemented for the early definitive diagnosis, robust preventive measures, and effective treatment modalities for NEC.


Asunto(s)
Apoptosis/fisiología , Enterocolitis Necrotizante/prevención & control , Eritropoyetina/fisiología , Factor I del Crecimiento Similar a la Insulina/fisiología , Telomerasa/metabolismo , Animales , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos BALB C
6.
Clin Oral Investig ; 25(9): 5403-5410, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33638713

RESUMEN

OBJECTIVES: The variation in the caries susceptibility while environmental factors are similar indicates that the effect of individual factors such as genetics on caries process and tooth development should be revealed. The aim of this study was to evaluate the association between genetic polymorphisms in MMP13 (rs2252070) and MMP20 (rs1784418) with caries experience. MATERIALS AND METHODS: A cross-sectional study was conducted on 200 subjects aged 6 to 14 years. Demographic data, data on oral health habits were obtained through the statements of guardian of the individuals, caries data was collected by clinical examination. Unstimulated whole saliva was collected to extract the genomic DNA. Genotyping of the selected polymorphisms was carried out by real-time PCR. Allele and genotype frequencies were compared between different subgroups considering caries experience. Data were analyzed using SPSS 16.0 by chi-square test and logistic regression analysis. RESULTS: Allele distribution of MMP13 was different between caries-affected and caries-free subjects. MMP13 A allele increased the caries risk (p=0.005, OR=1.84, 95% CI 1.20-2.82). Allele and genotype distribution of the polymorphism in MMP20 were not associated with caries experience (p>0.05). CONCLUSIONS: It is concluded that the genetic variation in MMP13 was associated with the caries experience in selected subjects in Turkey. CLINICAL RELEVANCE: The knowledge regarding association between the MMP genes and caries experience, might benefit the clinical practice, improving caries-preventive and caries-therapeutic approaches.


Asunto(s)
Susceptibilidad a Caries Dentarias , Caries Dental , Estudios Transversales , Caries Dental/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Metaloproteinasas de la Matriz , Polimorfismo Genético/genética , Polimorfismo de Nucleótido Simple
7.
Turk J Med Sci ; 51(4): 1775-1780, 2021 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-33581708

RESUMEN

Background/aim: Although cutting edge procedures such as cell-free fetal DNA isolation from maternal blood are now available, invasive prenatal tests are still being used extensively for prenatal diagnosis. The study aims to evaluate the demographic data, indications, and cytogenetic results of 9297 results of patients who underwent prenatal invasive testing for genetic analysis that were referred for the last 20 years in a University Medical Genetics Center. Materials and methods: The records of 8363 amniocenteses, 626 chorionic villus, and 308 cordocenteses samples were retrospectively evaluated and analyzed regarding referral reasons, indications and their cytogenetic results. The total numbers and the percentages of each group were recorded; Chi-square and logistic regression analyses were performed to give the statistical likelihood of different events. Results: The number of referrals decreased significantly after 2009. Risk of having trisomy 21 as well as trisomy 13 and 18 significantly increased in parallel with advanced maternal age. When the 21­25 age group was compared to the older age groups in terms of having a trisomy 21 pregnancy, the risk doubled in the 36­40, 5 times higher in 41­45 and 10-fold in 46­50 age groups. No significant linear correlation between maternal serum screening test results and trisomy 21 was found, however the difference between the pregnancies whom cut-off value above and below 1/250 in maternal serum screening test were significant. Conclusion: These data have provided useful information on the frequency of referrals to the reference genetics department, and the feasibility of genetic services. By reviewing the indications and their corresponding results, we can offer invaluable insights that will be useful in genetic counseling and also in the development of more effective genetic strategies.


Asunto(s)
Aberraciones Cromosómicas , Síndrome de Down , Asesoramiento Genético/métodos , Diagnóstico Prenatal/estadística & datos numéricos , Adulto , Aneuploidia , Femenino , Genética Médica , Humanos , Persona de Mediana Edad , Embarazo , Estudios Retrospectivos , Turquía/epidemiología , Universidades
8.
Ann Hum Genet ; 84(4): 324-330, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32162695

RESUMEN

INTRODUCTION: PTEN gene mutations are responsible for the PTEN hamartoma tumor syndrome (PHTS). In this study, clinical and molecular findings of patients carrying PTEN mutations are presented. Our aim is to contribute to genotype-phenotype correlation and define the most common findings of the syndrome in pediatric patients. METHODS AND MATERIALS: Ten molecularly confirmed PHTS patients from seven families were included in the study. All patients were examined by a clinical geneticist. Laboratory test results were obtained from hospital records. Sequencing of PTEN gene was performed. Variant interpretation was done in accordance with 2015 recommendations from the American College of Medical Genetics. RESULTS: Macrocephaly was the most common clinical finding, involving all patients. This was followed by skin lesions, neurodevelopmental delay, and pathologic cranial magnetic resonance imaging findings. Seven different heterozygous PTEN gene variants were found in seven families. Four of these were located in exon 5, which has been described as a hot spot area for the PTEN gene. Four mutations were novel. A wide range of phenotypic and genotypic spectra was found in our study group. CONCLUSION: Screening of PTEN mutations in patients with macrocephaly is recommended due to an increased risk of cancer. Further cases are needed to make a phenotype-genotype correlation in PHTS.


Asunto(s)
Síndrome de Hamartoma Múltiple/genética , Fosfohidrolasa PTEN/genética , Adolescente , Niño , Preescolar , Exones , Femenino , Genotipo , Síndrome de Hamartoma Múltiple/diagnóstico , Humanos , Lactante , Masculino , Mutación , Linaje , Fenotipo
9.
Neurourol Urodyn ; 39(2): 833-840, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31971631

RESUMEN

AIMS: In children with Down syndrome (DS) which causes cognitive impairment and intellectual disability (ID), dysfunctional voiding is proposed to be more common than in the normal population. In this study, we aimed to compare the voiding symptoms of DS children with a control group by validated questionnaires. METHODS: Thirty-seven DS children without any previous urological complaints and 59 non-DS healthy children as control group was included in the study. Overactive bladder symptoms and dysfunctional voiding were evaluated with validated Overactive Bladder Questionnaire (OAB-V8) and Dysfunctional Voiding Symptom Score (DVSS) questionnaire, respectively. Data were arranged, descriptive and comparative statistical analysis were performed. RESULTS: Demographic data of the two groups were similar except age of completing toilet training being higher in DS group. Total OAB-V8 and DVSS scores were significantly higher in the DS group. The mean scores of questions regarding voiding frequency, urgency and urgency incontinence in OAB-V8 were significantly higher in the DS group. The mean daytime incontinence, urgency, urgency incontinence, and quality of life scores in the DVSS were also significantly higher in the DS group. CONCLUSIONS: DS children have more frequent dysfunctional voiding than the normal population. ID of these children may prevent the expression of these symptoms. Awareness and early detection of these symptoms are crucial to prevent devastating complications such as renal failure. Therefore, validated questionnaires are simple, useful, and noninvasive methods.


Asunto(s)
Síndrome de Down/complicaciones , Vejiga Urinaria Hiperactiva/fisiopatología , Incontinencia Urinaria/fisiopatología , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Síntomas del Sistema Urinario Inferior/complicaciones , Síntomas del Sistema Urinario Inferior/fisiopatología , Masculino , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios , Vejiga Urinaria Hiperactiva/complicaciones , Incontinencia Urinaria/complicaciones , Micción
10.
Scand J Immunol ; 89(2): e12737, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30506560

RESUMEN

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by susceptibility to bacterial and fungal infections resulting from the inadequacy of phagocytic leucocytes to produce reactive oxygen radicals. CGD is a genetically heterogeneous disease with an X-linked recessive (XR-CGD) form caused by mutations in the CYBB (OMIM #300481) gene encoding the gp91(phox) protein, and an autosomal recessive (AR-CGD) form caused by mutations in the CYBA (OMIM #608508), NCF1 (OMIM #608512), NCF2 (OMIM #608515) and NCF4 (OMIM #601488) genes encoding p22(phox), p47(phox), p67(phox) and p40(phox), respectively. The genetic mutation of one of the cytosolic p47phox/p67phox proteins and membrane-bound gp91phox/p22phox proteins, which constitutes the NADPH oxidase enzyme complex, causes the disease. In this study, we evaluated the clinical, laboratory and genetic findings and the prognostic effects of molecular inheritance of our 24 CGD cases (14 XR, 10 autosomal recessive-AR). Consanguinity (three XR and all AR cases) showed statistically significant relationship with the type of hereditary inheritance (P < 0.001). 83% patients had an infection since early infancy. The mean age of initiation of symptoms was earlier in XR cases, and 78% patients had respiratory tract infections. Bone marrow transplantation was performed in five XR cases (two ex) and four AR (one ex) cases. Three of nine XR and two of six AR cases deceased on medical follow-up. In countries especially with high consanguinity rates, the early diagnosis for appropriate prophylactic treatment of CGD is quietly important to avoid from recurrent severe infections, early death and fatal complications of late transplantation.


Asunto(s)
Consanguinidad , Enfermedad Granulomatosa Crónica/inmunología , NADPH Oxidasas/metabolismo , Adolescente , Edad de Inicio , Trasplante de Médula Ósea , Niño , Preescolar , Femenino , Estudios de Seguimiento , Genes Recesivos/genética , Genes Ligados a X/genética , Enfermedad Granulomatosa Crónica/epidemiología , Enfermedad Granulomatosa Crónica/genética , Humanos , Masculino , Mutación/genética , NADPH Oxidasa 2/genética , Especies Reactivas de Oxígeno/metabolismo , Estudios Retrospectivos , Resultado del Tratamiento , Turquía/epidemiología
11.
Biol Sport ; 36(1): 9-16, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30899134

RESUMEN

The aim of this study was to determine the distribution of ACTN3 R577X gene polymorphism in soccer players and sedentary individuals, and to investigate the relationship of this distribution with performance tests. A total of 100 soccer players and 101 sedentary individuals were enrolled in the study. Standing long jump and countermovement jump (with arm swing, without arm swing and repeated) scores were recorded, using a jump meter. Maximum VO2 levels were measured using a treadmill-connected cardiopulmonary exercise device, Masterscreen CPX. ACTN3 R577X polymorphism was evaluated by real-time PCR. ACTN3 R577X genotype distribution was found to be similar in soccer players and controls (p>0.05). The only statistically significant finding was a shorter countermovement jump with arm swing scores in the RR-genotyped soccer players, compared with their RX genotyped counterparts (p<0.05). In the soccer player group, RX-genotyped subjects were observed to have lower respiratory threshold values compared with RR-genotyped subjects (p<0.05). No significant correlation was detected between this distribution and performance test results. ACTN3 R577X genotype distribution was found to have no effect on sprint and endurance characteristics in amateur soccer players. The ACTN3 R577X polymorphism may not be a specific enough genetic marker to determine athletic performance in soccer.

13.
Turk J Med Sci ; 48(4): 862-872, 2018 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-30119594

RESUMEN

Background/aim: Geographical distribution, ethnicity, and other socioeconomic factors may affect anthropometric measurements, and for that reason each society should determine their own measurements accounting for those factors. In this study, we aimed to determine the anthropometric measurements of healthy late preterm and term infants to compare the results with other national and international studies. Materials and methods: This sectional study was carried out among 1197 infants born with a gestational age of ≥35 weeks. Chest circumference, ear length, foot length, palmar length, middle finger length, philtrum distance, inner and outer canthal distances, and palpebral fissure length were measured in the first 24 h of life. Results: All measurements of late preterm infants were smaller than those of term infants (P ˂ 0.05). Compared with male infants, the chest circumference, ear length, foot length, palmar length, philtrum distance, and inner canthal distances of the female infants were lower (P ˂ 0.05). No significant differences were found between male and female infants' middle finger length, outer canthal distance, and palpebral fissure length measurements. Percentile values for all measurements of 35­42-week male and female infants were described. Conclusion: These measurements of male and female infants born between 35 and 42 weeks may be useful for early detection of syndromes by detecting anatomical abnormalities in our population.


Asunto(s)
Antropometría/métodos , Pesos y Medidas Corporales , Edad Gestacional , Recien Nacido Prematuro , Nacimiento Prematuro , Nacimiento a Término , Anomalías Congénitas/diagnóstico , Diagnóstico Precoz , Femenino , Pie , Mano , Cabeza , Humanos , Recién Nacido , Masculino , Valores de Referencia , Factores Sexuales , Tórax
15.
Hum Mol Genet ; 22(25): 5121-35, 2013 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-23906836

RESUMEN

Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs*53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategies.


Asunto(s)
Anomalías Múltiples/genética , Ensamble y Desensamble de Cromatina/genética , Cara/anomalías , Deformidades Congénitas del Pie/genética , Deformidades Congénitas de la Mano/genética , Hipotricosis/genética , Discapacidad Intelectual/genética , Micrognatismo/genética , Cuello/anomalías , Eliminación de Secuencia/genética , Anomalías Múltiples/patología , Adolescente , Adulto , Proteínas Portadoras/genética , Niño , Preescolar , Proteínas Cromosómicas no Histona/genética , Proteínas de Unión al ADN/genética , Exoma/genética , Cara/patología , Facies , Femenino , Deformidades Congénitas del Pie/patología , Deformidades Congénitas de la Mano/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hipotricosis/patología , Lactante , Recién Nacido , Discapacidad Intelectual/patología , Cariotipificación , Masculino , Micrognatismo/patología , Mutación Missense , Cuello/patología , Proteínas Represoras , Proteína SMARCB1 , Factores de Transcripción/genética
16.
Am J Med Genet A ; 167A(2): 400-2, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25487726

RESUMEN

LACHT syndrome, Lung Agenesis, Congenital Heart defects, and Thumb anomalies, (Mardini-Nyhan Association OMIM #601612) is a rare condition characterized by unilateral or bilateral lung agenesis, complex cardiac defects, especially anomalous pulmonary venous return, and thumb anomalies. Based on previous cases, its inheritance pattern seems to be autosomal recessive. In 1985, the syndrome was firstly described by Mardini and Nyhan in four patients from unrelated families. Until now, a total of eight patients have been reported in the literature. Molecular cause of the disease is still unknown. Here, we report on a patient with LACHT syndrome diagnosed by clinical findings. In this study, we present a 4.5-month-old female infant with right lung agenesis and inguinal hernia, in which ovaries are revealed on ultrasonography. The infant was born to consanguineous parents following a 38th week of gestation, with a birth weight of 2,800 g. Overall development was consistent with age; she had thumb abnormalities. Echocardiography showed peripheral pulmonary stenosis. The girl was diagnosed as LACHT syndrome based on the findings of unilateral lung agenesis, thumb anomalies, and peripheral pulmonary stenosis. LACHT syndrome should be considered in the differential diagnosis of patients with unilateral or bilateral lung agenesis. Here, we report on the 9th case in the literature. The consanguinity of the parents supports autosomal inheritance as the genetic basis of LACHT syndrome.


Asunto(s)
Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Fenotipo , Facies , Femenino , Humanos , Lactante , Radiografía Torácica , Síndrome
17.
Hemoglobin ; 39(4): 230-4, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26076395

RESUMEN

ß-Thalassemia (ß-thal) is the most common monogenic disorder in Turkey. The aim of this study was to investigate the spectrum of ß-thal mutations in the Aegean region of Turkey. The data was derived from 1171 unrelated ß-thal subjects, detected in a regional reference hospital between November 2004 and December 2013. Screening for the 22 common mutations was performed using the polymerase chain reaction (PCR)-reverse dot-blot method, and direct automated DNA sequencing for the unknown samples. Thirty-one different ß-thal alleles were identified. Seven mutations, namely IVS-I-110 (G > A) (41.7%), IVS-I-1 (G > A) (8.9%), IVS-II-745 (C > G) (8.6%), codon 8 (-AA) (7.7%), IVS-II-1 (G > A) (7.2%), IVS-I-6 (T > C) (6.6%), codon 39 (C > T) (4.6%) accounted for 85.3% of the mutated alleles. Frequencies of the remaining 24 ß-thal mutations were less than 2.2%; these included one novel mutation [HBB: c.206_212del (p.Leu69Profs*19)], and four others [-56 (G > C), codon 16 (-C), IVS-I (-3) (C > T) (codon 29), codon 76 (-C)] found in Turkey for the first time. The results will help to prevent severe ß-thal through genetic counseling and prenatal diagnosis (PND) in the Aegean region of Turkey.


Asunto(s)
Eliminación de Secuencia , Globinas beta/genética , Talasemia beta/genética , Alelos , Análisis Mutacional de ADN , Índices de Eritrocitos , Frecuencia de los Genes , Genotipo , Geografía , Humanos , Turquía , Talasemia beta/sangre , Talasemia beta/diagnóstico
18.
Hum Genet ; 133(1): 29-39, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23982343

RESUMEN

Proteoglycan (PG) synthesis begins with the sequential addition of a "linker chain", made up of four sugar residues, to a specific region of a core protein. Defects in the enzymes catalyzing steps two to four of the linker chain synthesis have been shown to cause autosomal recessive human phenotypes while no mutation has yet been reported in humans for the xylosyltransferases 1 and 2 (XT1 and XT2), the initiating enzymes in the linker chain formation. Here, we present a consanguineous Turkish family with two affected individuals presenting with short stature, distinct facial features, alterations of fat distribution, and moderate intellectual disability. X-rays showed only mild skeletal changes in the form of a short femoral neck, stocky and plump long bones and thickened ribs. Using a combination of whole-exome sequencing (WES), determination of homozygous stretches by WES variants, and classical linkage analysis, we identified the homozygous missense mutation c.C1441T in XYLT1, encoding XT1, within a large homozygous stretch on chromosome 16p13.12-p12.1. The mutation co-segregated with the phenotype in the family, is not found in over 13,000 alleles in the exome variant server and is predicted to change a highly conserved arginine at position 481 (p.R481W) located in the putative catalytical domain. Immunostaining of primary patient fibroblasts showed a loss of predominance of Golgi localization in mutant cells. Moreover, western blot analysis of decorin in cell culture supernatant demonstrated glycosylation differences between patient and control cells. Our data provide evidence that functional alterations of XT1 cause an autosomal recessive short stature syndrome associated with intellectual disability.


Asunto(s)
Enanismo/genética , Discapacidad Intelectual/genética , Pentosiltransferasa/genética , Consanguinidad , Exoma , Femenino , Genes Recesivos , Ligamiento Genético , Homocigoto , Humanos , Masculino , Mutación Missense , Linaje , Pentosiltransferasa/metabolismo , Fenotipo , Proteoglicanos/metabolismo , Análisis de Secuencia de ADN , Síndrome , Turquía , Rayos X , UDP Xilosa Proteína Xilosiltransferasa
19.
Am J Hum Genet ; 88(1): 30-41, 2011 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-21194678

RESUMEN

Microphthalmia with limb anomalies (MLA) is a rare autosomal-recessive disorder, presenting with anophthalmia or microphthalmia and hand and/or foot malformation. We mapped the MLA locus to 14q24 and successfully identified three homozygous (one nonsense and two splice site) mutations in the SPARC (secreted protein acidic and rich in cysteine)-related modular calcium binding 1 (SMOC1) in three families. Smoc1 is expressed in the developing optic stalk, ventral optic cup, and limbs of mouse embryos. Smoc1 null mice recapitulated MLA phenotypes, including aplasia or hypoplasia of optic nerves, hypoplastic fibula and bowed tibia, and syndactyly in limbs. A thinned and irregular ganglion cell layer and atrophy of the anteroventral part of the retina were also observed. Soft tissue syndactyly, resulting from inhibited apoptosis, was related to disturbed expression of genes involved in BMP signaling in the interdigital mesenchyme. Our findings indicate that SMOC1/Smoc1 is essential for ocular and limb development in both humans and mice.


Asunto(s)
Deformidades Congénitas de las Extremidades/genética , Microftalmía/genética , Osteonectina/genética , Animales , Secuencia de Bases , Mapeo Cromosómico , Cromosomas Humanos Par 14/genética , Codón sin Sentido/genética , Extremidades/crecimiento & desarrollo , Ojo/crecimiento & desarrollo , Genes Recesivos , Sitios Genéticos , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Datos de Secuencia Molecular , Nervio Óptico/anomalías , Empalme del ARN/genética , Síndrome de Waardenburg/genética
20.
Metab Brain Dis ; 29(3): 809-12, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24788897

RESUMEN

X linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease characterized by progressive demyelination of the central nervous system, adrenocortical insufficiency and elevated levels of very long chain fatty acids (VLCFAs). It is caused by mutations in ABCD1 gene located at Xq28. More than 1,300 mutations have been identified to date which is unique to each patient. In this study we report the mutational analysis of 2 X-ALD patients (1 male and 1 female) showing variable clinical spectrum. The mutation analysis of the female patient revealed IVS5-6delC (c.1489-6delC) and p. P543L variations in compound heterozygous state. The male patient was found to be hemizygous for a novel mutation, p. R104P. In conclusion, while defining a novel mutation, the cases presented herein may contribute to the mutation and clinical spectrum of X-ALD.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Adrenoleucodistrofia/genética , Mutación , Miembro 1 de la Subfamilia D de Transportador de Casetes de Unión al ATP , Niño , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA