Two different missense mutations of PEX genes in two similar patients with severe Zellweger syndrome: an argument on the genotype-phenotype correlation

2020 ◽  
Vol 33 (3) ◽  
pp. 437-441
Author(s):  
Cengiz Havali ◽  
Sevil Dorum ◽  
Yılmaz Akbaş ◽  
Orhan Görükmez ◽  
Tugba Hirfanoglu
Keyword(s):  
Missense Mutation ◽  
Zellweger Syndrome ◽  
Failure To Thrive ◽  
Severe Form ◽  
Oral Feeding ◽  
Missense Mutations ◽  
Multisystem Disease ◽  
Homozygous Missense Mutation ◽  
Peroxisomal Biogenesis ◽  
Severe Hypotonia

AbstractBackgroundPeroxisomal biogenesis disorders (PBDs) include a miscellaneous group of diseases which cause serious multisystem disease. Mutations of 13 different PEX genes lead to PBDs including Zellweger syndrome (ZS). Different types of mutations of PEX1 and PEX10 genes are correlated with broad-range phenotypes of PBDs.Case presentationPatient 1 is a 4-month-old boy who was affected by myoclonic seizures, poor oral feeding since birth. The patient was hypotonic and had hepatosplenomegaly. Patient 2 is a 2-month-old boy who presented with decreased movement, severe hypotonia and failure to thrive. The laboratory studies of the patients revealed increased plasma very-long-chain fatty acids (VLCFAs). The genetic analyses of patient 1 demonstrated the first homozygous missense mutation in the PEX10 gene. A novel homozygous missense mutation was found in the PEX1 gene in patient 2.ConclusionsThis report highlights that the detected homozygous missense mutations of PEX10 and PEX1 genes and the substitutions of specific amino acids lead to the severe form of PBDs.

scholarly journals Zellweger syndrome: Depiction of MRI findings in early infancy at 3.0 Tesla

2017 ◽  
Vol 30 (5) ◽  
pp. 442-444 ◽  
Author(s):  
Cory M Pfeifer ◽  
Carlos A Martinot
Keyword(s):  
Neuronal Migration ◽  
Autosomal Recessive ◽  
Zellweger Syndrome ◽  
Severe Form ◽  
Mri Findings ◽  
3.0 Tesla ◽  
Peroxisomal Biogenesis ◽  
Patient At Risk ◽  
Rare Autosomal Recessive Disease ◽  
Peroxisomal Biogenesis Disorders

Zellweger syndrome, also referred to as cerebrohepatorenal syndrome, is a rare autosomal recessive disease representing the most severe form of the peroxisomal biogenesis disorders. Neuroanatomical sequelae include impaired neuronal migration, diffuse hypomyelination, and sensorineural degeneration. Due to the rare and severe nature of this disorder, early mortality, and comorbidities that place the patient at risk for sedated imaging, high-resolution magnetic resonance imaging findings of Zellweger syndrome are scarce in the literature. Presented here is a case of this rare disease imaged at 3.0 Tesla.

A Novel Mutation Glyl672→Arg in Type 2A and a Homozygous Mutation in Type 2B von Willebrand Disease

1996 ◽  
Vol 76 (02) ◽  
pp. 253-257 ◽  
Author(s):  
Takeshi Hagiwara ◽  
Hiroshi Inaba ◽  
Shinichi Yoshida ◽  
Keiko Nagaizumi ◽  
Morio Arai ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Novel Mutation ◽  
Point Mutations ◽  
Japanese Patients ◽  
Von Willebrand Disease ◽  
Homozygous Mutation ◽  
Missense Mutations ◽  
Reaction Products ◽  
Type 3 ◽  
Von Willebrand

SummaryGenetic materials from 16 unrelated Japanese patients with von Willebrand disease (vWD) were analyzed for mutations. Exon 28 of the von Willebrand factor (vWF) gene, where point mutations have been found most frequent, was screened by various restriction-enzyme analyses. Six patients were observed to have abnormal restriction patterns. By sequence analyses of the polymerase chain-reaction products, we identified a homozygous R1308C missense mutation in a patient with type 2B vWD; R1597W, R1597Q, G1609R and G1672R missense mutations in five patients with type 2A; and a G1659ter nonsense mutation in a patient with type 3 vWD. The G1672R was a novel missense mutation of the carboxyl-terminal end of the A2 domain. In addition, we detected an A/C polymorphism at nucleotide 4915 with HaeIII. There was no particular linkage disequilibrium of the A/C polymorphism, either with the G/A polymorphism at nucleotide 4391 detected with Hphl or with the C/T at 4891 detected with BstEll.

scholarly journals Incidence of the CHEK2 Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 470
Author(s):  
Danuta Gąsior-Perczak ◽  
Artur Kowalik ◽  
Krzysztof Gruszczyński ◽  
Agnieszka Walczyk ◽  
Monika Siołek ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Missense Mutation ◽  
Vascular Invasion ◽  
Germline Mutations ◽  
Primary Treatment ◽  
Clinicopathological Characteristics ◽  
Missense Mutations ◽  
Papillary Thyroid ◽  
Treatment Responses

The CHEK2 gene is involved in the repair of damaged DNA. CHEK2 germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether CHEK2 germline mutations predict a worse clinical course for PTC. The study included 1547 unselected PTC patients (1358 women and 189 men) treated at a single center. The relationship between mutation status and clinicopathological characteristics, treatment responses, and disease outcome was assessed. CHEK2 mutations were found in 240 (15.5%) of patients. A CHEK2 I157T missense mutation was found in 12.3%, and CHEK2 truncating mutations (IVS2 + 1G > A, del5395, 1100delC) were found in 2.8%. The truncating mutations were more common in women (p = 0.038), and were associated with vascular invasion (OR, 6.91; p < 0.0001) and intermediate or high initial risk (OR, 1.92; p = 0.0481) in multivariate analysis. No significant differences in these parameters were observed in patients with the I157T missense mutation. In conclusion, the CHEK2 truncating mutations were associated with vascular invasion and with intermediate and high initial risk of recurrence/persistence. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease.

Homozygous missense mutation in BOLA3 causes multiple mitochondrial dysfunctions syndrome in two siblings

2012 ◽  
Vol 36 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Tobias B. Haack ◽  
Boris Rolinski ◽  
Birgit Haberberger ◽  
Franz Zimmermann ◽  
Jessica Schum ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Mitochondrial Dysfunctions ◽  
Homozygous Missense Mutation

Identification of a novel missense mutation in Brazilian patient with a severe form of mucopolysaccharidosis type IVA

2013 ◽  
Vol 108 (2) ◽  
pp. S59-S60
Author(s):  
Sandra Leistner-Segal ◽  
Francyne Kubaski ◽  
Ana Carolina Brusius-Facchin ◽  
Heloísa M.C. Palhares ◽  
Marly Aparecida Spadotto Balarin ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Severe Form ◽  
Mucopolysaccharidosis Type ◽  
Brazilian Patient ◽  
Mucopolysaccharidosis Type Iva

scholarly journals First description of phosphofructokinase deficiency in spain: identification of a novel homozygous missense mutation in the PFKM gene

2013 ◽  
Vol 4 ◽  
Author(s):  
Joan-Lluis Vives-Corrons ◽  
Pavla Koralkova ◽  
Josep M. Grau ◽  
Maria del Mar Mañú Pereira ◽  
Richard Van Wijk
Keyword(s):  
Missense Mutation ◽  
Homozygous Missense Mutation ◽  
Phosphofructokinase Deficiency

scholarly journals Atypical pyridoxine dependent epilepsy resulting from a new homozygous missense mutation, in ALDH7A1

Seizure ◽  
2018 ◽  
Vol 57 ◽  
pp. 32-33 ◽  
Author(s):  
Zahraa Haidar ◽  
Nadine Jalkh ◽  
Sandra Corbani ◽  
Ali Fawaz ◽  
Eliane Chouery ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Homozygous Missense Mutation

scholarly journals ACO2 homozygous missense mutation associated with complicated hereditary spastic paraplegia

2018 ◽  
Vol 4 (2) ◽  
pp. e223 ◽  
Author(s):  
Christian G. Bouwkamp ◽  
Zaid Afawi ◽  
Aviva Fattal-Valevski ◽  
Inge E. Krabbendam ◽  
Stefano Rivetti ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Hereditary Spastic Paraplegia ◽  
Krebs Cycle ◽  
Spastic Paraplegia ◽  
Homozygous Carrier ◽  
Clinical Genetic ◽  
Homozygous Missense Mutation ◽  
Recessive Mutations ◽  
Mitochondrial Aconitase ◽  
Essential Enzyme

ObjectiveTo identify the clinical characteristics and genetic etiology of a family affected with hereditary spastic paraplegia (HSP).MethodsClinical, genetic, and functional analyses involving genome-wide linkage coupled to whole-exome sequencing in a consanguineous family with complicated HSP.ResultsA homozygous missense mutation was identified in the ACO2 gene (c.1240T>G p.Phe414Val) that segregated with HSP complicated by intellectual disability and microcephaly. Lymphoblastoid cell lines of homozygous carrier patients revealed significantly decreased activity of the mitochondrial aconitase enzyme and defective mitochondrial respiration. ACO2 encodes mitochondrial aconitase, an essential enzyme in the Krebs cycle. Recessive mutations in this gene have been previously associated with cerebellar ataxia.ConclusionsOur findings nominate ACO2 as a disease-causing gene for autosomal recessive complicated HSP and provide further support for the central role of mitochondrial defects in the pathogenesis of HSP.

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