Clinical, biochemical and genotypical characteristics in biotinidase deficiency

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Abdurrahman Akgun ◽  
Askin Sen ◽  
Hasan Onal
Keyword(s):  
Autosomal Recessive ◽  
Vision Loss ◽  
Study Data ◽  
Biotinidase Deficiency ◽  
Enzyme Deficiency ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
The Central Nervous System

Abstract Objectives Hypotonia, lethargy, eczema, alopecia, conjunctivitis, ataxia, hearing loss, optic atrophy, cognitive retardation, and seizures can occur in patients with biotinidase deficiency, and it is inherited as autosomal recessive. The aim of this study was to evaluate the cases followed up with the diagnosis of biotinidase deficiency in our unit, in terms of clinical, biochemical and genetic analyses. Methods A total of 112 cases followed up in our centre with the diagnosis of biotinidase deficiency between August 2018–September 2020 were included in the study. Data were collected retrospectively. Results A total of 112 cases (55.4% male, mean age: 2.2 ± 2.8 years) diagnosed with biotinidase deficiency were evaluated. Diagnoses were made by newborn screening in 90.2% of the cases, by family screening in 4.5%, and by investigating symptoms in 5.4%. The most frequently (27.5%) detected mutations were c.1330G>C (p.D444H)/c.1330G>C (p.D444H) homozygous mutation, followed by (13.0%) c.1330G>C (p.D444H)/c.470G>A (p.R157H) compound heterozygous mutation, and (13.0%) c.470G>A (p.R157H)/c.470G>A (p.R157H) homozygous mutation. Biotinidase enzyme levels were found to be higher in patients with the p.D444H homozygous mutation than patients with other mutations. Biotin treatment was started in all patients with enzyme deficiency. Conclusions Since the treatment is inexpensive and easily available, it is vital to detect this disease before symptom onset, especially findings related to the central nervous system, hearing and vision loss. In patients diagnosed with enzyme deficiency, the diagnosis should be definitively confirmed by genetic analysis.

scholarly journals Expanding the genotype-phenotype spectrum of autosomal recessive Charcot-Marie-Tooth disease: A novel PLEKHG5 gene mutation

2021 ◽  
Vol 26 (3) ◽  
pp. 607-612
Author(s):  
Özlem Yayici Köken ◽  
Ülkühan Öztoprak ◽  
Vehap Topçu ◽  
Büsranur Çavdarli ◽  
Çagri Mesut Temucin ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Disease Type ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Pleckstrin Homology Domain ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Motor Neuropathy ◽  
Charcot Marie Tooth ◽  
Type C

Autosomal recessive intermediate Charcot Marie Tooth (CMT) disease type C is a very rarely-seen neurogenetic disorder. Homozygous or compound heterozygous mutation in the Pleckstrin homology domain-containing family G member 5 (PLEKHG5) gene on chromosome 1p36 was recently reported in patients with CMT. From the first description of the disease to date, almost 40 different variants associated with the PLEKHG5 gene were identified. Here, we present an adolescent girl who was thought initially to be myopathy because of progressive proximal muscle weakness. The electrophysiologic study revealed axonal sensory and motor neuropathy with some demyelinating features. She was diagnosed with autosomal recessive inheritance, intermediate CMT disease type C with a novel homozygous mutation in the PLEKHG5 gene in clinical exome sequencing as c.1600- 2A>G by next-generation sequencing. We describe here the novel mutation in the PLEKHG5 gene and the genotype-phenotype correlation.

scholarly journals Novel compound heterozygous mutation in SACS gene leads to a milder autosomal recessive spastic ataxia of Charlevoix‐Saguenay, ARSACS , in a Finnish family

2016 ◽  
Vol 4 (12) ◽  
pp. 1151-1156 ◽  
Author(s):  
Johanna Palmio ◽  
Mikko Kärppä ◽  
Peter Baumann ◽  
Sini Penttilä ◽  
Jukka Moilanen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Spastic Ataxia

scholarly journals BETA-GLOBIN GENE MUTATIONS IN TURKISH CHILDREN WITH BETA-THALASSEMIA: RESULTS FROM A SINGLE CENTER STUDY

2013 ◽  
Vol 5 (1) ◽  
pp. e2013055 ◽  
Author(s):  
Ali Fettah ◽  
Cengiz Bayram ◽  
Nese Yarali ◽  
Pamir Isik ◽  
Abdurrahman Kara ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Thalassemia Intermedia ◽  
Turkish Children ◽  
Tertiary Center

Introduction: The beta thalassemias are common genetic disorders in Turkey and in this retrospective study our aim was to evaluate β-globin chain mutations and the phenotypic severity of β-thalassemia patients followed-up in our hospital, a tertiary center which serves patients from all regions of Turkey. Materials and Methods: 106 pediatric patients were analysed for β-globin gene mutations by using DNA analysis. Patients were classified as having β-thalassemia major or β-thalassemia intermedia based on age at diagnosis, transfusion frequency and lowest hemoglobin concentration in between transfusions. Results: There were 106 patients (52.8% female and 47.2% male) with a mean age of 11.2±5 years (1.6 – 22.3 years). Eighty-four (79.2%) patients had β-thalassemia major, whereas the remaining 22 patients (20.8%) were identified as having β-thalassemia intermedia. Overall, 18 different mutations were detected on 212 alleles. The most frequently encountered mutation was IVS I.110 (G>A) (35.3%), followed by Codon 8 del-AA (10.4%), IVS II.1 (G>A) (8%), IVS I.1 (G>A) (7.5%), Codon 39 (C>T) (7.1%) and Codon 5 (-CT) (6.6%), which made up 79.4% of observed mutations. According to present results, IVS I.110 (G>AA) was the most frequent mutation observed in this study, as in other results from Turkey. Evaluation of β-thalassemia mutations in 106 patients with 212 alleles, revealed the presence of homozygous mutation in 85 patients (80.2%) and compound heterozygous mutation in 21 patients (19.8%). The mutations detected in patients with homozygous mutation were IVS I.110 (G>A) (38.8%), Codon 8 del –AA (11.8%), IVS II.1 (G>A) (8.2%) and IVS I.1 (G>A) (8.2%). Observed mutations in the compound heterozygotes were Codon 39 (C>T)/Codon 41-42 (-CTTT) (14.3%), IVS I.110 (G>A)/Codon 39(C>T) (14.3%), IVS I.110 (G>A)/Codon 44(-C) (14.3%), and IVS II.745 (C>G)/ 5’UTR + 22 (G>A) (9.5%). Conclusion: Our hospital is a tertiary referral center that provides care to patients from all over the country, and thus the distribution of mutations observed in the current study is significant in term of representing that of the country as a whole.

scholarly journals Nonlethal Raine Syndrome in a Newborn Boy Caused by a Novel FAM20C Variant

2021 ◽  
pp. 1-5
Author(s):  
Nazan Eras ◽  
Yalcin Celik
Keyword(s):  
Genetic Disorder ◽  
Bone Dysplasia ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Limited Information ◽  
Sequencing Platform ◽  
Gene Sequence Analysis ◽  
Raine Syndrome

Raine syndrome (RS) is a rare genetic disorder characterized by osteosclerotic bone dysplasia caused by a homozygous mutation, compound heterozygous mutation, or microdeletion in the FAM20C gene. In the present study, the MiSeq next-generation sequencing platform was used to perform the FAM20C gene sequence analysis. A novel homozygous variant c.1255T>C (p.W419R) in the FAM20C gene was diagnosed, and a nonlethal RS phenotype was confirmed, thus contributing to the expansion of the nonlethal RS phenotype. Since there is limited information about rare diseases, we believe that these studies will contribute to the literature and to the understanding of how these disorders develop and progress.

Clinical and molecular genetic characterization of two patients with mutations in the phosphoglucomutase 1 (PGM1) gene

2018 ◽  
Vol 31 (7) ◽  
pp. 781-788 ◽  
Author(s):  
Yu Ding ◽  
Niu Li ◽  
Gouying Chang ◽  
Juan Li ◽  
Ruen Yao ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Chinese Han ◽  
Targeted Gene Sequencing ◽  
Molecular Genetic Characterization

Abstract Background The phosphoglucomutase 1 (PGM1) enzyme plays a central role in glucose homeostasis by catalyzing the inter-conversion of glucose 1-phosphate and glucose 6-phosphate. Recently, PGM1 deficiency has been recognized as a cause of the congenital disorders of glycosylation (CDGs). Methods Two Chinese Han pediatric patients with recurrent hypoglycemia, hepatopathy and growth retardation are described in this study. Targeted gene sequencing (TGS) was performed to screen for causal genetic variants in the genome of the patients and their parents to determine the genetic basis of the phenotype. Results DNA sequencing identified three variations of the PGM1 gene (NM_002633.2). Patient 1 had a novel homozygous mutation (c.119delT, p.Ile40Thrfs*28). In patient 2, we found a compound heterozygous mutation of c.1172G>T(p.Gly391Val) (novel) and c.1507C>T(p.Arg503*) (known pathogenic). Conclusions This report deepens our understanding of the clinical features of PGM1 mutation. The early molecular genetic analysis and multisystem assessment were here found to be essential to the diagnosis of PGM1-CDG and the provision of timely and proper treatment.

New Compound Heterozygous Mutations of GPIIb in Patient with Glanzmann Thrombasthenia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3921-3921
Author(s):  
Ziqiang Yu ◽  
Jian Su ◽  
Xia Bai ◽  
Zhaoyue Wang ◽  
Changgeng Ruan
Keyword(s):  
Flow Cytometry ◽  
Autosomal Recessive ◽  
Protein Translation ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Sequencing Analysis ◽  
Glanzmann Thrombasthenia ◽  
Compound Heterozygous Mutations ◽  
Average Fluorescence

Abstract Glanzmann thrombasthenia (GT) is a homozygous or compound heterozygous autosomal recessive bleeding disorder caused by the qualitative or quantitative deficiency of integrin GPIIb-IIIa, which acts as the receptor of platelet fibrinogen. Here we report a case of GT with a compound heterozygous mutation in GPIIb according to the results of flow cytometry and genetic investigation.The flow cytometry was used to measure the average amounts of integrin GPIIb-IIIa on the patient’s platelets, and all 30 exons of GPIIb were amplified and sequenced with the corresponding primers.The average fluorescence intensity of integrin GPIIb-IIIa were 3.07 and 12.5, respectively, compared with 23.7 and 254, respectively, in the normal healthy individuals. And sequencing analysis of all exons of GPIIb demonstrated that there existed following compound heterozygous mutations in GPIIb gene: one heterozygote mutation (68 C→A) in the 1st exon, which resulted in Pro 23 His substitution in signal peptide domain; one nonsense heterozygous mutation (1750 C→T) in the 17th exon, which result in premature termination; one heterozygote mutation (2159 T→C) in the 21stexon, which resulted in Leu 720 Pro substitution. According to Glanzmann thrombasthenia database of ISTH (http://sinaicentral.mssm.edu/intranet/research/glanzmann/listmutations?mut=GPIIb), 68 C→A mutation and 2159 T→C mutation are novel mutations in the GPIIb heavy chain. These compound heterozygous mutations in GPIIb gene might be a novel pathogenetic mechanism of GT, which impaired the protein translation and co-expression with GPIIIa on the membrane of platelet.

scholarly journals Novel compound heterozygous mutation in the CNGA1 gene underlie autosomal recessive retinitis pigmentosa in a Chinese family

2016 ◽  
Vol 36 (1) ◽  
Author(s):  
Xin Jin ◽  
Ling-Hui Qu ◽  
Bao-Ke Hou ◽  
Hai-Wei Xu ◽  
Xiao-Hong Meng ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Recessive ◽  
Protein Product ◽  
Compound Heterozygous Mutation ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Rod Photoreceptors ◽  
Gene Coding ◽  
Compound Mutation

A novel compound mutation in CNGA1 gene, coding for the cGMP-gated ion channel protein, results in a protein product that is not targeted to the plasma membrane, which would be deleterious to rod photoreceptors leading to retinitis pigmentosa (RP).

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