Novel ABCD1 gene mutations in Iranian pedigrees with X-linked adrenoleukodystrophy

Abstract Background X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disorder, is caused by mutations in the ABCD1 gene located on Xq28. X-ALD is characterized by a spectrum of different manifestations varying in patients and families. Methods Four pedigrees with X-ALD consisting of patients and healthy members were selected for investigation of ABCD1 gene mutations. The mutation analysis was performed by polymerase chain reaction (PCR) followed by direct sequencing of all exons. The identified mutations were investigated using bioinformatics tools to predict their effects on the protein product and also to compare the mutated sequence with close species. Results One previously known missense mutation (c.1978 C > T) and three novel mutations (c.1797dupT, c.879delC, c.1218 C > G) were identified in the ABCD1 gene, each in one family. Predicting the effects of the mutations on protein structure and function indicated the probable damaging effect for them with significant alterations in the protein structure. We found three novel mutations in the ABCD1 gene with damaging effects on its protein product and responsible for X-ALD.

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First Place—Resident Clinical Science Award 1997: Germline screening of the NF-2 gene in families with unilateral vestibular schwannoma

Otolaryngology ◽

10.1016/s0194-5998(98)70166-4 ◽

1998 ◽

Vol 119 (1) ◽

pp. 1-6 ◽

Cited By ~ 9

Author(s):

Paul H. Bikhazi ◽

Anil K. Lalwani ◽

Eugene J. Kim ◽

Nadim Bikhazi ◽

Ali Attaie ◽

...

Keyword(s):

Vestibular Schwannoma ◽

Direct Sequencing ◽

Gene Mutations ◽

Neurofibromatosis Type ◽

Germline Mutations ◽

Type Ii ◽

Chain Reaction ◽

Neurofibromatosis Type Ii ◽

Polymerase Chain ◽

Head Neck

Vestibular schwannoma may present clinically in two forms: sporadic unilateral or hereditary bilateral. Familial transmission of vestibular schwannoma is known to occur only in neurofibromatosis type II (NF-2). We have previously described the clinical characteristics of unilateral vestibular schwannoma presenting in families, in the absence of ther criteria necessary for the diagnosis of NF-2. Polymerase chain reaction–single strand chain polymorphism was used to screen for germline NF-2 gene mutations in six families with unilateral vestibular schwannoma. Direct sequencing of DNA from blood was done in affected subjects from three families. No germline mutations were identified. Because NF-2 gene mutations are detected in only 33% of patients with NF-2, hereditary transmission of mutations cannot be entirely excluded. However, in the absence of germline mutations in the NF-2 gene, familial occurrence of unilateral vestibular schwannoma more likely represents either a chance somatic NF-2 gene mutation or originates from a separate genetic loci. (Otolaryngol Head Neck Surg 1998;119:1–6.)

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Korelasi Genotip-Fenotip Pasien Talasemia Beta Di Kota Samarinda Kalimantan Timur Tahun 2019

Buletin Penelitian Kesehatan ◽

10.22435/bpk.v48i2.2362 ◽

2020 ◽

Vol 48 (2) ◽

pp. 91-98

Author(s):

Zaenal Adi Susanto ◽

Wahyu Siswandari ◽

Lantip Rujito

Keyword(s):

Polymerase Chain Reaction ◽

Dna Analysis ◽

Statistical Tests ◽

Direct Sequencing ◽

Gene Mutations ◽

Beta Thalassemia ◽

Chain Reaction ◽

Spearman Rank ◽

Blood Disorder ◽

Polymerase Chain

Abstract Thalassemia is a genetic blood disorder that is autosomal recessive and is quite common throughout the world. This study aims to determine the relationship of Hemoglobin beta (HBB) gene mutations types with clinical levels and hematological in the subjects of 31 thalassemia-beta patients in Samarinda City. Blood samples were taken from patients to obtain their DNA then amplified them with the Polymerase Chain Reaction and direct sequencing techniques to analyze the hemoglobin-beta gene mutation. Javanese ethnics is the most dominant in this study (64.5%) and the most common clinical levels is the moderate category (77.4%). The mean MCV and MCH values were 72±5,5 fL and 24±3,3 pg. DNA analysis found 8 types of mutant alleles including 48.4% of Cd26 / HbE (GAG>AAG), 14.5% of IVS-1-5 (G>C) 12.9% of IVS-1-2 (T>C, ,8.1% of Cd35 (-C) , 6.5% of IVS-1-1 (G>T) 3.2% of Cd30 (AGG>ACG) , Cd60 (GTG>GAG) and Cd2 (CAT>CAC ) are 1.6% each. This study found mutations that had not been previously reported in Indonesia, namely Cd60 (GTG>GAG) and Cd2 (CAT>CAC). Spearman rank statistical tests show there is no significant relationship between the two studied variables. Keyword: Beta-thalassemia mutation, Clinical levels, Hematological Abstrak Talasemia merupakan salah satu kelainan darah genetik yang bersifat autosomal resesif dan cukup banyak ditemui di seluruh dunia. Diperkirakan 3-10 persen masyarakat Indonesia adalah pembawa sifat talasemia dengan berbagai macam latar belakang etnik. Studi ini bertujuan untuk mengetahui hubungan jenis mutasi gen hemoglobin beta (HBB) dengan derajat klinis dan pemeriksaan darah pada 31 pasien talasemia-beta di Kota Samarinda Provinsi Kalimantan Timur pada bulan Mei tahun 2019. Sampel darah pasien diambil untuk memperoleh DNA kemudian dilakukan amplifikasi dengan Polymerase Chain Reaction dan dilakukan teknik direct sekuensing untuk menganalisis mutasi gen hemoglobin-beta. Etnik Jawa merupakan yang dominan dalam penelitian ini (64,5%) dan derajat klinis paling umum adalah kategori sedang (77,4%). Rerata nilai MCV dan MCH masing-masing adalah 72±5,5 fL dan 24±3,3 pg. Analisa DNA didapatkan 8 jenis alel mutan yaitu Cd26/HbE (GAG>AAG) 48,4% selanjutnya IVS-1-5 (G>C) 14,5%, IVS-1-2 (T>C) 12,9%, Cd35 (-C) 8,1%, IVS-1-1 (G>T) 6,5%, Cd30 (AGG>ACG) 3,2%, Cd60 (GTG>GAG) dan Cd2 (CAT>CAC) masing-masing 1,6%. Studi ini menemukan mutasi yang belum dilaporkan pada penelitian sebelumnya di Indonesia yaitu Cd60 (GTG>GAG) dan Cd2 (CAT>CAC). Uji statistik spearman rank menunjukkan tidak terdapat hubungan bermakna antara ke dua variabel yang diteliti. Kata kunci: Mutasi talasemia beta, Derajat klinis, Hematologis

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Short lifetime structures appearing in RNA and DNA

Briefings in Functional Genomics ◽

10.1093/bfgp/ely035 ◽

2018 ◽

Vol 18 (3) ◽

pp. 174-181

Author(s):

Koichi Nishigaki

Keyword(s):

Restriction Enzymes ◽

Structure And Function ◽

Chain Reaction ◽

Single Stranded Conformation Polymorphism ◽

The Past ◽

Polymerase Chain ◽

Transient Structures ◽

And Function ◽

Rna And Dna ◽

Conformation Polymorphism

Abstract The structure and function of unstable single-stranded DNA (ssDNA) have not been widely examined. While numerous studies have investigated DNA as an information molecule, the different potentials of DNA, particularly those of ssDNA, remain unclear. For polypeptides, the significance of denatured structures has been established in the past two decades. Polynucleotides have chemically distinct properties from polypeptides, but their behaviours have not been thoroughly studied. In this review, three different phenomena related to unstable ssDNA are discussed: i) ssDNA cleavage of restriction enzymes; ii) single-stranded conformation polymorphism, which can be theoretically explained by single-stranded conformation dynamics; and iii) random PCR (Polymerase Chain Reaction). These features can be utilized for scientific or technical applications. Previous studies showed that the phenomena exhibited by ssDNA were correctly understood only when unstable and transient structures were taken into account. Transient structures of ssDNA may have undiscovered functions governed by very rapid processes and/or multi-diversity states because of their intrinsic natures.

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Alstrom Syndrome with Novel ALMS1 Mutations: A Case Report

Experimental and Clinical Endocrinology & Diabetes Reports ◽

10.1055/s-0043-109433 ◽

2017 ◽

Vol 04 (01) ◽

pp. e10-e13

Author(s):

Lanrong Liu ◽

Hong Li ◽

Lixin Shi

Keyword(s):

Sanger Sequencing ◽

Venous Blood ◽

Gene Mutations ◽

Chinese Child ◽

Novel Mutations ◽

Chain Reaction ◽

Alström Syndrome ◽

Alstrom Syndrome ◽

Polymerase Chain ◽

Pathogenic Gene

Abstract Objective To report novel mutations of ALMS1 and evaluate clinical characteristics in the Chinese Child with Alstrom syndrome (ALMS). Methods The Child and his parents were examined clinically and venous blood was collected. ALMSl gene analysis was carried out using DNA Sanger sequencing. Using polymerase chain reaction (PCR) amplified ALMS1 gene exons and splice sequence. The objective products were directly sequenced and analyzed. Pathogenic gene mutations were identified by contrast with the transcript (GRCh37/hg19). Results The Child had typical clinical features of Alstrom syndrome. Sequencing the ALMS1 gene confirmed 2 novel heterozygous non-sense mutations in exon8, c.4600C>T (p.Q1534X) and in exon16, c.11410C>T (p.R3804X), respectively, resulting in premature protein truncation. Conclusions 2 novel heterozygous non-sense mutations were identified in the Chinese Child with Alstrom syndrome, expanding the ALMS1 gene mutations causing Alstrom syndrome.

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In silicoanalysis of coding SNPs and 3′-UTR associated miRNAs inDCAF17gene that may affect the regulation and pathogenesis of Woodhouse-Sakati Syndrome

10.1101/601310 ◽

2019 ◽

Author(s):

Abdelrahman H. Abdelmoneim ◽

Asia M. Elrashied ◽

Alaa I. Mohammed ◽

Sara A. Mirghani ◽

Rania E. Osman ◽

...

Keyword(s):

Diabetes Mellitus ◽

Protein Structure ◽

In Silico Analysis ◽

Structure And Function ◽

Novel Mutations ◽

Inherited Disorders ◽

Bioinformatics Tools ◽

Extrapyramidal Signs ◽

And Function ◽

Silico Analysis

AbstractBackgroundWoodhouse-Sakati Syndrome refers to a group of inherited disorders characterized by alopecia, hypogonadism, diabetes mellitus, hypothyroidism and progressive extrapyramidal signs. The aim of this study is to identify the pathogenic SNPs in theDCAF17gene with their related mciroRNAs and their effect on the structure and function of the protein.Material and MethodsWe used different bioinformatics tools to predict the effect of each SNP on the structure and function of the protein. After that we defined the miRNAs founded in the 3′-UTR region on theDCAF17gene and studied the annotations relative to it.ResultsTen deleterious SNPs out of 339 were found to have a damaging effect on the protein structure and function, with one significant micoRNA in the 3′-UTR region.ConclusionThis was the first in silico analysis ofDCAF17gene, in which 10 novel mutations were found using different bioinformatics tools that could be used as a diagnostic markers for Woodhouse-Sakati syndrome, with one relevant microRNA that can regulate the function of the protein.

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