scholarly journals A Novel Mutation of ATP7B Gene in a Case of Wilson Disease

Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 123
Author(s):  
Cigdem Yuce Kahraman ◽  
Ali Islek ◽  
Abdulgani Tatar ◽  
Özlem Özdemir ◽  
Adil Mardinglu ◽  
...  
Keyword(s):  
Wilson Disease ◽  
Novel Mutation ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Compound Heterozygous ◽  
Atp7b Gene ◽  
Loss Of Function ◽  
Clinical Presentations ◽  
The Family ◽  
The Brain

Wilson disease (WD) (OMIM# 277900) is an autosomal recessive inherited disorder characterized by excess copper (Cu) storage in different human tissues, such as the brain, liver, and the corneas of the eyes. It is a rare disorder that occurs in approximately 1 in 30,000 individuals. The clinical presentations of WD are highly varied, primarily consisting of hepatic and neurological conditions. WD is caused by homozygous or compound heterozygous mutations in the ATP7B gene. The diagnosis of the disease is complicated because of its heterogeneous phenotypes. The molecular genetic analysis encourages early diagnosis, treatment, and the opportunity to screen individuals at risk in the family. In this paper, we reported a case with a novel, hotspot-located mutation in WD. We have suggested that this mutation in the ATP7B gene might contribute to liver findings, progressing to liver failure with a loss of function effect. Besides this, if patients have liver symptoms in childhood and/or are children of consanguineous parents, WD should be considered during the evaluation of the patients.

scholarly journals Clinical case of a rare neurodegenerative disease with iron accumulation in the brain, type 4, in a 15-year-old child

2019 ◽  
Vol 64 (5) ◽  
pp. 109-113
Author(s):  
I. F. Fedoseeva ◽  
T. V. Poponnikova ◽  
G. Yu. Galieva ◽  
S. V. Moschnegootz
Keyword(s):  
Amino Acid ◽  
Neurodegenerative Disease ◽  
Autosomal Recessive ◽  
Clinical Case ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Compound Heterozygous ◽  
Resonance Imaging ◽  
The Brain ◽  
Progressive Course

The authors presented f clinical and genetic description and analysis of a rare autosomal recessive neurodegenerative disease with an accumulation of iron in the brain, type 4. The disease began in adolescence and has a slowly progressive course. The diagnosis was confirmed by magnetic resonance imaging and molecular genetic analysis. The author found two compound heterozygous mutations in the C19оrf12 gene: in exon 3 (chr 19: 30193873C>T, rs515726205), leading to a substitution of the amino acid in the 69th position of the protein (p.Gly69Arg, NM_001031726.3), and the mutation in the 3rd exon (chr19: 30193806A>T) not described earlier, resulting in the replacement of the amino acid in 91 positions of the protein (p.Lеu91Gln, NM_001031726.3).

scholarly journals Characterization of a novel CSF1R mutation causing hereditary diffuse leukoencephalopathy with spheroids in a case presenting with young-onset dementia

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S118-S118
Author(s):  
Walid Nasr ◽  
Mahmoud Gad ◽  
Tareq Qassem
Keyword(s):  
Novel Mutation ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Insertion Mutation ◽  
Heterozygous Deletion ◽  
Young Onset ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Young Onset Dementia ◽  
Rapid Cognitive Decline

ObjectiveThis poster aims to report an unregistered mutation CSF1R gene in a patient presenting young-onset dementia.Hypothesis: Novel heterozygous deletion–insertion mutation in the Colony-Stimulating Factor 1 Receptor (CSF1R) gene is linked to a case of hereditary diffuse leukoencephalopathy with spheroids (HDLS), presenting with young-onset dementia.BackgroundCSF1R mediates proliferation, differentiation, and survival of monocytes/ macrophages and microglia. Pathogenic variants in the CSF1R gene cause autosomal dominant diffuse hereditary leukoencephalopathy with spheroids characterized by variable behavioural, cognitive, and motor changes, usually presenting with young-onset dementia. The average lifespan after the start of the symptoms is often 6 years.Case reportMolecular genetic analysis of whole-exome sequencing (WES) was carried out for a 49-year-old male patient presenting with rapid cognitive decline, behavioural symptoms and impaired sphincteric control.DiscussionWES identified the heterozygous deletion–insertion variant c.2356_2357delinsAC p.(Leu786Thr) (chr5:149435867-49435868; hg19) in the CSF1R gene. To the best of our knowledge the variant has not been described in the literature so far (HGMD 2019.3). No allele frequencies in the general population have been documented.ConclusionWe believe that we have identified a novel mutation in the CSF1R gene. This mutation is likely to be linked to this patient presenting with young-onset dementia.

The complete description of larval stages of the lobster shrimpLeonardsaxius amurensis(Kobjakova, 1937) (Decapoda: Axiidea: Axiidae) identified by DNA barcoding

2017 ◽  
Vol 98 (6) ◽  
pp. 1435-1453 ◽  
Author(s):  
Elena S. Kornienko ◽  
Darya D. Golubinskaya ◽  
Olga M. Korn ◽  
Svetlana N. Sharina
Keyword(s):  
Larval Development ◽  
Sequence Data ◽  
Molecular Genetic ◽  
Sympatric Species ◽  
Molecular Genetic Analysis ◽  
Mitochondrial Coi ◽  
Larval Stages ◽  
The Family ◽  
Rdna Sequence Data ◽  
First Time

The complete larval development of the lobster shrimpLeonardsaxius amurensis(Kobjakova, 1937) (Decapoda: Axiidea: Axiidae) is described and illustrated for the first time. The first zoeae of this species were collected from the plankton samples and reared in the laboratory before moulting to the megalopa. A molecular genetic analysis based on comparison of partial mitochondrial COI, 12S rDNA and 16S rDNA sequence data confirmed the identity of axiid larvae found in the plankton andL. amurensisadults collected in the same area. The larval development ofL. amurensisincludes five zoeal stages and a single megalopa. Zoeae I ofL. amurensisare characterized by the presence of one short posterodorsal spine on the fifth pleonite in contrast to the larvae of related sympatric speciesBoasaxius princepshaving four posterodorsal spines on the pleonites 2–5.Leonardsaxius amurensisoccupies an intermediate position between lobster shrimps with abbreviated pelagic development (2–3 zoeal stages) and species with long development (up to eight zoeal stages). Thus, the number of zoeal stages in the family Axiidae varies widely, similarly to that in the families Callianassidae and Upogebiidae.

Morphological and molecular identification of some species of nematode of the family Protostrongylidae Leiper, 1926

2016 ◽  
Vol 3 (4) ◽  
pp. 454-461
Author(s):  
Салахутдинов ◽  
I. Salakhutdinov ◽  
Рузиев ◽  
B. Ruziev ◽  
Каримова ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Phylogenetic Trees ◽  
Molecular Genetic ◽  
Digital Camera ◽  
Molecular Genetic Analysis ◽  
Nucleotide Sequences ◽  
Genetic Identification ◽  
Mountain Area ◽  
Phylogenetic Relations ◽  
The Family

Objective of research: conducting morphological and molecular-genetic identification and studying phylogenetic relations between protostrongylids. Materials and methods: helminthological material was collected from wild (Capra sibirica, C. falconeri, Ovis vignei and O. ammon) and domestic hollow horned ruminants (C. hircus and O. aries), and land mollusks of the family Xeropicta in the piedmont and mountain area of Uzbekisan. The morphology of protostrongylids was studied using the methods of Boev (1975) and Anderson (1978). To identify the nematode type we used temporary preparations treated with glycerol. The first-stage larvae were investigated by examination of fecal samples from animals taking into account the length, tail form and body size. To study the morphology of the third-stage protostrongylid larvae the feet of infected mollusks Xeropicta candaсharica were separated and placed into the artificial gastric juice where the cap was destroyed and the infected larvae were eliminated. After determination of species belonging of mature and larval nematodes the material was stored in separate test-tubes with distilled water under the low temperature (- 20 ºС) or in 70 % Ethanol for the molecular analysis. We used microscopes ML 2000 with a digital camera and Olympus CX3. DNA extraction, amplification and sequencing were performed with an automated sequencer. Phylogenetic analysis was conducted using the software Clustal X 2.0. Phylogenetic trees were created by the Neighbor–Joining method. Nucleotide sequences ITS-2 regions of species Protostrongylus rufescens (EU018485), P. shiozawai (AB478249), Ortostrongylus macrotis (EU018483), Cystocaulus ocreatus (EU018481) and Umingmakstrongylus pallikuukensis (AY648409) received from the NCBI GenBank were used in phylogenetic analysis. Results and discussion: Four species of adult protostrongylid nematodes: Protostrongylus rufescens, P. hobmaieri, Spiculocaulus leuckarti and Cystocaulus ocreatus were determined. DNA from four species of mature protostrongylids and larvae was amplified by using ITS-2 regions. Amplificate dimension of nematodes P. rufescens and P. hobmaieri was 380 base pairs (b.p.), S. leuckarti – 388, C. ocreatus – 399 b.p. According to the results of phylogenetic analysis and comparison of nucleotide sequences, five protostrongylid species were found in animals of the Caprinae subfamily: P. rufescens, P. hobmaieri, Protostrongylus sp., S. leuckarti and C. ocreatus. The morphological and molecular-genetic analysis of detected nematodes enables the precise identification.

scholarly journals Molecular Genetic Analysis of FOXL2 Gene in Two Iranian Families with Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Nooshin Asgari ◽  
Mohammad Taghi Akbari ◽  
Faravareh Khordadpoor Deilamani ◽  
Gholamreza Babamohammadi
Keyword(s):  
Novel Mutation ◽  
Direct Sequencing ◽  
Genetic Disorder ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Premature Menopause ◽  
Type I ◽  
Forkhead Transcription Factor ◽  
Salting Out ◽  
Foxl2 Gene

Background: Blepharophimosis-ptosis-epicanthus syndrome (BPES) is a rare genetic disorder with autosomal dominant inheritance. There are two distinct phenotypes: BPES type I, which is associated with eyelid abnormalities as well as female infertility or premature menopause due to ovarian resistance to gonadotropins, whereas in type II only eyelid abnormalities are present. Mutations in the forkhead transcription factor 2 (FOXL2) gene are responsible for both types of BPES. Objectives: The purpose of this study was to identify mutations in FOXL2 in two Iranian families (from Tehran) with BPES who were referred to Tehran Medical Genetics laboratory. Methods: The peripheral blood was collected from the affected members of two BPES families and genomic DNA was extracted using salting out method. Then, direct sequencing of whole exon of FOXL2 genewas performed. Results: Two frameshift mutations were identified in FOXL2 gene in two familial cases including NM_023067:c.102_103insA (p.G35Rfs*61)as a novel mutation and NM_023067:c.855_871dup (p.H291Rfs*71) (17-bp insertion). Both mutations cause the protein to be truncated and are responsible for a severe phenotype (BPES type I) which was in harmony with our finding. Conclusions: Our results increased the spectrum of FOXL2 mutations and confirm the mutations associated with BPES type I.

Characterization of plasminogen variants in healthy subjects and plasminogen mutants in patients with inherited plasminogen deficiency by isoelectric focusing gel electrophoresis

2004 ◽  
Vol 92 (08) ◽  
pp. 352-357 ◽  
Author(s):  
Katrin Tefs ◽  
Maria Georgieva ◽  
Stefan Seregard ◽  
Campbell Tait ◽  
Lori Luchtman-Jones ◽  
...  
Keyword(s):  
Isoelectric Focusing ◽  
Gel Electrophoresis ◽  
Healthy Subjects ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Molecular Genetic Analysis ◽  
Compound Heterozygous ◽  
Wild Type ◽  
Ligneous Conjunctivitis

SummaryPlasmin(ogen) plays an important role in fibrinolysis and wound healing. Severe hypoplasminogenemia has recently been linked to ligneous conjunctivitis. Plasminogen (plg) is known as a polymorphic protein and most of these variants have been identified using isoelectric focusing (IEF) gel electrophoresis. Here, we studied common plg variants from healthy subjects and plg mutants from three patients with hypoplasminogenemia and three subjects with dysplasminogenemia by molecular genetic analysis and IEF. Analysis of 24 healthy subjects showed that subjects with the most common IEF plg phenotype A (n = 12) were homozygous for aspartate at position 453 (453D), while both subjects with IEF plg phenotype B were homozygous for asparagine at this position (453N). Subjects with IEF plg phenotype AB (n = 10) were compound-heterozygous for 453D/453N. Three patients with severe hypoplasminogenemia and different plg gene mutations exhibited characteristic “abnormal” IEF band patterns when compared with IEF plg phenotypes A and B. In all heterozygous family members the observed IEF plg phenotype was derived from the wild type plg molecule only, probably due to low concentration of the mutant plg molecule in plasma. In contrast, in three unrelated subjects with heterozygous dysplasminogenemia an equal “mixture” of wild type and mutant plg was found by IEF analysis. In conclusion, plg phenotyping by IEF in combination with molecular analysis of the plg gene seems to be a useful method for characterization of plg variants and mutants.

scholarly journals Study of molecular basis of thyroid dysgenesis

2018 ◽  
Vol 14 (2) ◽  
pp. 64-71
Author(s):  
Nina A. Makretskaya ◽  
Olga B. Bezlepkina ◽  
Anna A. Kolodkina ◽  
Alexey V. Kiyaev ◽  
Evgeny V. Vasilyev ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Molecular Basis ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Ion Torrent ◽  
Loss Of Function ◽  
Thyroid Dysgenesis ◽  
Different Types ◽  
Generation Sequencing ◽  
Tsh Levels

Congenital hypothyroidism is a heterogeneous group of diseases, which is manifested by loss of function of the thyroid gland that affects infants from birth. 80–85% of cases are due to different types of thyroid dysgenesis. 5 genes have been described that are involved in the pathogenesis of thyroid dysgenesis: TSHR, PAX8, FOXE1, NKX2-1, NKX2-5. Aims. To evaluate the prevalence of mutations in the genes TSHR, PAX8, FOXE1, NKX2-1, NKX2-5 among patients with severe congenital hypothyroidism. Materials and methods. 161 patients (64 boys, 97 girls) with congenital hypothyroidism (TSH levels at neonatal screening or retesting greater than 90 mU/l) were included in the study. 138 subjects had different variants of thyroid dysgenesis, and 23 patients had normal volume of the gland. A next generation sequencing was used for molecular-genetic analysis. Sequencing was performed using PGM semiconductor sequencer (Ion Torrent, Life Technologies, USA) and a panel “Hypothyroidism” (Custom DNA Panel). Assessment of the pathogenicity of sequence variants were carried out according to the latest international guidelines (ACMG, 2015). Results. 13 patients had variants in thyroid dysgenesis genes (8,1%, 13/161): TSHR, n = 6; NKX2-1, n = 3; NKX2-5, n = 1; PAX8, n = 3; FOXE1, n = 0. Conclusions. Mutations in thyroid dysgenesis genes are a rare pathology. The majority of variants among our patients were identified in TSHR.

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