scholarly journals A 12-Year-Old Girl with Bilateral Coats Disease and ABCA4 Gene Mutation

2018 ◽  
Vol 9 (2) ◽  
pp. 375-380 ◽  
Author(s):  
Ali Osman Saatci ◽  
Ziya Ayhan ◽  
Aylin Yaman ◽  
Elcin Bora ◽  
Ayfer Ulgenalp ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Gene Mutation ◽  
Laser Photocoagulation ◽  
Functional Result ◽  
Systemic Disease ◽  
Gene Mutations ◽  
Dexamethasone Implant ◽  
Single Session ◽  
Abca4 Gene ◽  
Coats Disease

A 12-year-old girl with bilateral stage 2B Coats disease was screened meticulously for a possible underlying systemic disease as she was female and the disease was bilateral. Full systemic workout turned out to be unremarkable. However, an ABCA4 gene mutation was found in the genetic analysis. NDP and TINF2 gene mutations were not present. She was successfully treated with a bilateral, single intravitreal injection of dexamethasone implant and a single session of indirect laser photocoagulation with a relatively good anatomic and functional result. To the best of our knowledge, the present case is the only reported case of Coats disease with an ABCA4 gene mutation.

scholarly journals Novel Genetic Findings in a Chinese Family with Axenfeld-Rieger Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Kuanshu Li ◽  
Liu Yang ◽  
Ying Liu ◽  
Ding Lin
Keyword(s):  
Genetic Counseling ◽  
Genetic Analysis ◽  
Gene Mutation ◽  
Genomic Dna ◽  
Gene Mutations ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Specific Therapy ◽  
Rieger Syndrome

Purpose. To describe a Chinese family with Axenfeld-Rieger syndrome (ARS) and report our novel genetic findings.Methods. Nine members of the same family underwent complete ophthalmologic examinations and genetic analysis. Genomic DNA was isolated from veinal blood and amplifed using PCR; the products of PCR were sequenced and compared with FOXC1 and PITX2 genes, from which the mutations were found.Results. Through the ophthalmologic examinations, 8 subjects were diagnosed as ARS and 1 subject was normal. A homozygous mutation c.1139_1141dupGCG(p.Gly380_Ala381insGly) and a heterozygous mutation c.1359_1361dupCGG(p.Gly456_Gln457insGly) in FOXC1 were identified in all subjects. The mutation (c.-10-30T>C) was identified in PITX2 in subjects III-1 and III-3.Conclusions.We found novel gene mutations in a Chinese family with ARS, which provides us with a better understanding of the gene mutation spectrum of ARS and the assistance for the genetic counseling and gene-specific therapy in the future.

scholarly journals The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome

2020 ◽  
Vol 21 (21) ◽  
pp. 8403
Author(s):  
Erkut Ilaslan ◽  
Renata Markosyan ◽  
Patrick Sproll ◽  
Brian J. Stevenson ◽  
Malgorzata Sajek ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Signaling Pathway ◽  
Gene Mutation ◽  
Gene Mutations ◽  
Androgen Insensitivity Syndrome ◽  
Homologous Gene ◽  
Gene Encoding ◽  
Androgen Insensitivity ◽  
Disorder Of Sexual Development ◽  
Partial Androgen Insensitivity Syndrome

Androgen insensitivity syndrome (AIS), manifesting incomplete virilization in 46,XY individuals, is caused mostly by androgen receptor (AR) gene mutations. Therefore, a search for AR mutations is a routine approach in AIS diagnosis. However, some AIS patients lack AR mutations, which complicates the diagnosis. Here, we describe a patient suffering from partial androgen insensitivity syndrome (PAIS) and lacking AR mutations. The whole exome sequencing of the patient and his family members identified a heterozygous FKBP4 gene mutation, c.956T>C (p.Leu319Pro), inherited from the mother. The gene encodes FKBP prolyl isomerase 4, a positive regulator of the AR signaling pathway. This is the first report describing a FKBP4 gene mutation in association with a human disorder of sexual development (DSD). Importantly, the dysfunction of a homologous gene was previously reported in mice, resulting in a phenotype corresponding to PAIS. Moreover, the Leu319Pro amino acid substitution occurred in a highly conserved position of the FKBP4 region, responsible for interaction with other proteins that are crucial for the AR functional heterocomplex formation and therefore the substitution is predicted to cause the disease. We proposed the FKBP4 gene as a candidate AIS gene and suggest screening that gene for the molecular diagnosis of AIS patients lacking AR gene mutations.

scholarly journals NPHS2 gene mutation, atopy, and gender as risk factors for steroid-resistant nephrotic syndrome in Indonesians

2011 ◽  
Vol 51 (5) ◽  
pp. 272 ◽  
Author(s):  
Dedi Rachmadi ◽  
Danny Hilmanto ◽  
Ponpon Ijradinata ◽  
Abdurahman Sukadi
Keyword(s):  
Risk Factors ◽  
Nephrotic Syndrome ◽  
Gene Mutation ◽  
Significant Risk ◽  
Gene Mutations ◽  
Male Gender ◽  
Amplification Refractory Mutation System ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Nphs2 Gene

Background Steroid-resistant nephrotic syndrome (SRNS) often develops into end stage renal disease. Previous studies have reported that NPHS2 gene mutation, gender, and atopic history are risk factors associated with SRNS. Interethnic, sociocultural, and environmental differences have also been suggested to affect these mutations.Objective To analyze possible risk factors for SRNS, including NPHS2 gene mutations (412C→T and 419delG), gender and atopic history, in Indonesian subjects with SRNS.Methods A case-control study with 153 subjects, consisting of 88 SRNS patients and 65 control subjects, was undertaken in 10 Indonesian teaching centre hospitals from September 2006 to December 2007. Analysis of the NPHS2 gene mutation in 412 C→T was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), while that for the NPHS2 gene mutation in 419delG was performed by restriction fragment length polymorphism (RFLP). Data was analyzed by multiple logistic regression.Results In our Indonesian subjects, the significant risk factors for SRNS were male gender (OR=2.21; CI 95%:1.07-4.56, P=0.036), NPHS2 412C→T gene mutation (OR=18.07; CI 95%:6.76-48.31, P<0.001), and NPHS2 419delG gene mutation (OR=4.55; CI 95%:1.66-12.47, P=0.003). However, atopic history was not a significant risk factor for SRNS (OR=1.807; CI 95%:0.642-5.086, P=0.262).Conclusion NPHS2 412C→T and 419delG gene mutations, as well as male gender are risk factors for SRNS in Indonesian subjects. Atopic history was not significantly associated with SRNS in our subjects. [Paediatr Indones. 2011;51:272-6].

scholarly journals The patient profile of individuals with Alpha-1 antitrypsine gene mutations at a referral center in Brazil

2018 ◽  
Vol 44 (5) ◽  
pp. 383-389
Author(s):  
Manuela Brisot Felisbino ◽  
Frederico Leon Arrabal Fernandes ◽  
Maria Cecília Nieves Maiorano de Nucci ◽  
Regina Maria de Carvalho Pinto ◽  
Emilio Pizzichini ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Respiratory Symptoms ◽  
Gene Mutations ◽  
Lower Lobe ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Referral Center ◽  
Patient Profile ◽  
Significant Difference ◽  
Alpha 1 Antitrypsin

ABSTRACT Objective: The clinical, functional, radiological and genotypic descriptions of patients with an alpha-1 antitrypsin (A1AT) gene mutation in a referral center for COPD in Brazil. Methods: A cross-sectional study of patients with an A1AT gene mutation compatible with deficiency. We evaluated the A1AT dosage and genotypic, demographic, clinical, tomographic, and functional characteristics of these patients. Results: Among the 43 patients suspected of A1AT deficiency (A1ATD), the disease was confirmed by genotyping in 27 of them. The A1AT median dosage was 45 mg/dL, and 4 patients (15%) had a normal dosage. Median age was 54, 63% of the patients were male, and the respiratory symptoms started at the age of 40. The median FEV1 was 1.37L (43% predicted). Tomographic emphysema was found in 77.8% of the individuals. The emphysema was panlobular in 76% of them and 48% had lower lobe predominance. The frequency of bronchiectasis was 52% and the frequency of bronchial thickening was 81.5%. The most common genotype was Pi*ZZ in 40.7% of participants. The other genotypes found were: Pi*SZ (18.5%), PiM1Z (14.8%), Pi*M1S (7.4%), Pi*M2Z (3.7%), Pi*M1I (3.7%), Pi*ZMnichinan (3.7%), Pi*M3Plowell (3.7%), and Pi*SF (3.7%). We did not find any significant difference in age, smoking load, FEV1, or the presence of bronchiectasis between the groups with a normal and a reduced A1AT dosage, neither for 1 nor 2-allele mutation for A1ATD. Conclusions: Our patients presented a high frequency of emphysema, bronchiectasis and bronchial thickening, and early-beginning respiratory symptoms. The most frequent genotype was Pi*ZZ. Heterozygous genotypes and normal levels of A1AT also manifested significant lung disease.

scholarly journals Children with 5′-end NF1 gene mutations are more likely to have glioma

2017 ◽  
Vol 3 (5) ◽  
pp. e192 ◽  
Author(s):  
Corina Anastasaki ◽  
Stephanie M. Morris ◽  
Feng Gao ◽  
David H. Gutmann
Keyword(s):  
Gene Mutation ◽  
Statistical Significance ◽  
Gene Mutations ◽  
Neurofibromatosis Type ◽  
Published Data ◽  
Data Sets ◽  
Nonsense Mutations ◽  
Data Set ◽  
Nf1 Gene ◽  
The Relationship

Objective:To ascertain the relationship between the germline NF1 gene mutation and glioma development in patients with neurofibromatosis type 1 (NF1).Methods:The relationship between the type and location of the germline NF1 mutation and the presence of a glioma was analyzed in 37 participants with NF1 from one institution (Washington University School of Medicine [WUSM]) with a clinical diagnosis of NF1. Odds ratios (ORs) were calculated using both unadjusted and weighted analyses of this data set in combination with 4 previously published data sets.Results:While no statistical significance was observed between the location and type of the NF1 mutation and glioma in the WUSM cohort, power calculations revealed that a sample size of 307 participants would be required to determine the predictive value of the position or type of the NF1 gene mutation. Combining our data set with 4 previously published data sets (n = 310), children with glioma were found to be more likely to harbor 5′-end gene mutations (OR = 2; p = 0.006). Moreover, while not clinically predictive due to insufficient sensitivity and specificity, this association with glioma was stronger for participants with 5′-end truncating (OR = 2.32; p = 0.005) or 5′-end nonsense (OR = 3.93; p = 0.005) mutations relative to those without glioma.Conclusions:Individuals with NF1 and glioma are more likely to harbor nonsense mutations in the 5′ end of the NF1 gene, suggesting that the NF1 mutation may be one predictive factor for glioma in this at-risk population.

scholarly journals Usher syndrome gene mutation spectrum in Russian patients

2020 ◽  
pp. 38-39
Author(s):  
М.Е. Иванова ◽  
А.М. Демчинский ◽  
В.С. Каймонов ◽  
И.В. Миронова ◽  
И.В. Володин ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Retinitis Pigmentosa ◽  
Gene Mutation ◽  
Clinical Diagnosis ◽  
Usher Syndrome ◽  
Gene Mutations ◽  
Mutation Spectrum ◽  
Initial Sample ◽  
New Mutations

Изучение спектра мутаций и совершенствование диагностики синдрома Ашера (СА) особо актуальны в связи с разрабатываемыми подходами к генной терапии заболевания. Среди 46 пациентов с признаками СА патогенные мутации выявлены нами у 40 (87%) пациентов. СА I и II типов определены у 26% и 57% пробандов исходной выборки, соответственно. У пациентов с СА I выявлены мутации в генах MYO7A (73%), CDH23 (7%), PCDH15 (7%), и USH1C (13%). Наибольшую частоту показала мутация MYO7A p.Q18*. Описано 6 новых мутаций в гене MYO7A, и две - в гене PCDH15. У пациентов с СА II выявлена 21 мутация гена USH2A, 5 из которых описаны впервые. Наибольшую частоту показала мутация USH2A p.W3955*. У двух пациентов выявлены мутации в генах несиндромального пигментного ретинита RHO и RPGR, что позволило уточнить клинический диагноз. Studying the mutation spectrum and improvement of molecular verification of the Usher syndrome (USH) are of particular relevance as gene therapy emerges. Among 46 patients with signs of Usher syndrome we identified mutations in 40 (85%) patients, establishing a diagnosis of USH1 and USH2 for 26% and 57% of the probands of the initial sample, respectively. Patients with USH1 showed mutations in the MYO7A (73%), CDH23 (7%), PCDH15 (7%), and USH1C (13%) genes. MYO7A p.Q18* mutation showed the highest frequency. We have identified 6 new mutations in the MYO7A gene, and 2 in the PCDH15 gene. In USH2 patients, 21 USH2A gene mutations were identified, 5 of which are novel. The USH2A mutation p.W3955* was most frequent. Two patients showed mutations in the non-syndromic retinitis pigmentosa genes RHO and RPGR, which made it possible to clarify the clinical diagnosis.

scholarly journals A severe recessive and a mild dominant form of Charcot-Marie-Tooth disease associated with a newly identified Glu222Lys GDAP1 gene mutation.

2014 ◽  
Vol 61 (4) ◽  
Author(s):  
Dagmara Kabzińska ◽  
Katarzyna Kotruchow ◽  
Joanna Cegielska ◽  
Irena Hausmanowa-Petrusewicz ◽  
Andrzej Kochański
Keyword(s):  
Genetic Counseling ◽  
Gene Mutation ◽  
Autosomal Dominant ◽  
Clinical Course ◽  
Axonal Neuropathy ◽  
Gene Mutations ◽  
Special Importance ◽  
Recessive Trait ◽  
Dominant Form ◽  
Charcot Marie Tooth

Charcot-Marie-Tooth (CMT) disease caused by mutations in the GDAP1 gene has been shown to be inherited via traits that may be either autosomal recessive (in the majority of cases) [CMT4A] or autosomal dominant [CMT2K]. CMT4A disease is characterized by an early onset, and a severe clinical course often leading to a loss of ambulation, whereas CMT2K is characterized by a mild clinical course of benign axonal neuropathy beginning even in the 6th decade of life. Clinical data from a GDAP1 mutated patient suggests that the presence of a particular mutation is associated with a certain trait of inheritance. The association of a particular GDAP1 gene mutation and a dominant or recessive trait of inheritance is of special importance for genetic counseling and the prenatal diagnostics as regards severe forms of CMT. In the present study we report on two CMT families in which a newly identified Glu222Lys mutation within the GDAP1 gene segregates both in autosomal dominant and recessive traits. Our study shows that at least some GDAP1 gene mutations may segregate with the CMT phenotype as both dominant and recessive traits. Thus, genetic counseling for CMT4A/CMT2K families requires more extensive data on GDAP1 phenotype-genotype correlations.

Sign in / Sign up

Export Citation Format

Share Document