scholarly journals Novel PRKAG2 variant presenting as liver cirrhosis: report of a family with 2 cases and review of literature

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Zahra Beyzaei ◽  
Fatih Ezgu ◽  
Bita Geramizadeh ◽  
Alireza Alborzi ◽  
Alireza Shojazadeh
Keyword(s):  
Liver Cirrhosis ◽  
Genetic Defect ◽  
Laboratory Data ◽  
Gene Sequencing ◽  
Adenosine Monophosphate ◽  
Heart Tissue ◽  
Regulatory Subunit ◽  
Autosomal Dominant Disorder ◽  
Heterozygous Variant ◽  
Targeted Gene Sequencing

Abstract Background Mutations in the PRKAG2 gene encoding the 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK), specifically in its γ2 regulatory subunit, lead to Glycogen storage disease of heart, fetal congenital disorder (PRKAG2 syndrome). These mutations are rare, and their functional roles have not been fully elucidated. PRKAG2 syndrome is autosomal dominant disorder inherited with full penetrance. It is characterized by the accumulation of glycogen in the heart tissue, which is clinically manifested as hypertrophic cardiomyopathy. There is little knowledge about the characteristics of this disease. This study reports a genetic defect in an Iranian family with liver problems using targeted-gene sequencing. Case presentation A 4-year-old girl presented with short stature, hepatomegaly, and liver cirrhosis. As there was no specific diagnosis made based on the laboratory data and liver biopsy results, targeted-gene sequencing (TGS) was performed to detect the molecular basis of the disease. It was confirmed that this patient carried a novel heterozygous variant in the PRKAG2 gene. The echocardiography was a normal. Conclusion A novel heterozygous variant c.592A > T (p.Met198Leu) expands the mutational spectrum of the PRKAG2 gene in this family. Also, liver damage in patients with PRKAG2 syndrome has never been reported, which deserves further discussion.

Identification of a novel mutation in the PHKA2 gene in a child with liver cirrhosis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Zahra Beyzaei ◽  
Fatih Ezgu ◽  
Mohammad Hadi Imanieh ◽  
Bita Geramizadeh
Keyword(s):  
Liver Cirrhosis ◽  
Metabolic Diseases ◽  
Novel Mutation ◽  
Laboratory Data ◽  
Glycogen Storage ◽  
Hepatic Involvement ◽  
Glycogen Storage Diseases ◽  
Novel Variant ◽  
Severe Liver Damage ◽  
Targeted Gene Sequencing

Abstract Objectives Glycogen storage diseases (GSDs) are heterogeneous disorders caused by various enzyme deficiencies. GSD type IX α2, the most common subtype of GSD IX, is due to a deficiency of hepatic phosphorylase kinase. Herein we will report a novel mutation in this disease with an unusual presentation. Case presentation we describe a 3-year-old boy who suffered from hepatomegaly, fatty liver disease, and liver cirrhosis. The cause of cirrhosis at a young age was unknown based on the laboratory data and liver biopsy, so we performed a targeted-gene sequencing (TGS) covering 450 genes involved in inborn metabolic diseases consisting of glycogen storage disorders genes with hepatic involvement. He was found out to have a rare novel pathogenic variant in the PHKA2 gene. Conclusions This novel variant c.2226+2T > C expands the mutational spectrum of the PHKA2 gene. Also, severe liver damage (cirrhosis) in patients with GSD- IX α2 has rarely been reported, which needs further discussion. We hypothesize that unidentified PHKA2 variants may be a rare cause of childhood liver cirrhosis.

scholarly journals Clinical and genetic spectrum of glycogen storage disease in Iranian population using targeted gene sequencing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zahra Beyzaei ◽  
Fatih Ezgu ◽  
Bita Geramizadeh ◽  
Mohammad Hadi Imanieh ◽  
Mahmood Haghighat ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Molecular Genetic ◽  
Gene Sequencing ◽  
Glycogen Storage ◽  
Loss Of Function ◽  
Retrospective Case ◽  
Complex Disorders ◽  
Glycogen Storage Diseases ◽  
Targeted Gene Sequencing ◽  
Retrospective Case Study

AbstractGlycogen storage diseases (GSDs) are known as complex disorders with overlapping manifestations. These features also preclude a specific clinical diagnosis, requiring more accurate paraclinical tests. To evaluate the patients with particular diagnosis features characterizing GSD, an observational retrospective case study was designed by performing a targeted gene sequencing (TGS) for accurate subtyping. A total of the 15 pediatric patients were admitted to our hospital and referred for molecular genetic testing using TGS. Eight genes namely SLC37A4, AGL, GBE1, PYGL, PHKB, PGAM2, and PRKAG2 were detected to be responsible for the onset of the clinical symptoms. A total number of 15 variants were identified i.e. mostly loss-of-function (LoF) variants, of which 10 variants were novel. Finally, diagnosis of GSD types Ib, III, IV, VI, IXb, IXc, X, and GSD of the heart, lethal congenital was made in 13 out of the 14 patients. Notably, GSD-IX and GSD of the heart-lethal congenital (i.e. PRKAG2 deficiency) patients have been reported in Iran for the first time which shown the development of liver cirrhosis with novel variants. These results showed that TGS, in combination with clinical, biochemical, and pathological hallmarks, could provide accurate and high-throughput results for diagnosing and sub-typing GSD and related diseases.

scholarly journals Author Correction: Clinical and genetic spectrum of glycogen storage disease in Iranian population using targeted gene sequencing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zahra Beyzaei ◽  
Fatih Ezgu ◽  
Bita Geramizadeh ◽  
Mohammad Hadi Imanieh ◽  
Mahmood Haghighat ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Gene Sequencing ◽  
Glycogen Storage ◽  
Iranian Population ◽  
Targeted Gene Sequencing

scholarly journals Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
John Hoon Rim ◽  
Se Hee Kim ◽  
In Sik Hwang ◽  
Soon Sung Kwon ◽  
Jieun Kim ◽  
...  
Keyword(s):  
Molecular Diagnosis ◽  
Early Onset ◽  
Gene Sequencing ◽  
Efficient Strategy ◽  
Targeted Gene Sequencing

scholarly journals Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test

2017 ◽  
Vol 20 (4) ◽  
pp. 435-443 ◽  
Author(s):  
Anath C Lionel ◽  
Gregory Costain ◽  
Nasim Monfared ◽  
Susan Walker ◽  
Miriam S Reuter ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genetic Test ◽  
Diagnostic Yield ◽  
Gene Sequencing ◽  
Whole Genome ◽  
Targeted Gene Sequencing

scholarly journals Role of type 2A phosphatase regulatory subunit B56α in regulating cardiac responses to β-adrenergic stimulation in vivo

2018 ◽  
Vol 115 (3) ◽  
pp. 519-529 ◽  
Author(s):  
Sarah-Lena Puhl ◽  
Kate L Weeks ◽  
Alican Güran ◽  
Antonella Ranieri ◽  
Peter Boknik ◽  
...  
Keyword(s):  
Systolic Dysfunction ◽  
Heart Tissue ◽  
Left Ventricular ◽  
Regulatory Subunit ◽  
Adrenergic Stimulation ◽  
Hypertrophic Response ◽  
Cardiac Responses ◽  
Cardiac Phenotype ◽  
And Function

Abstract Aims B56α is a protein phosphatase 2A (PP2A) regulatory subunit that is highly expressed in the heart. We previously reported that cardiomyocyte B56α localizes to myofilaments under resting conditions and translocates to the cytosol in response to acute β-adrenergic receptor (β-AR) stimulation. Given the importance of reversible protein phosphorylation in modulating cardiac function during sympathetic stimulation, we hypothesized that loss of B56α in mice with targeted disruption of the gene encoding B56α (Ppp2r5a) would impact on cardiac responses to β-AR stimulation in vivo. Methods and results Cardiac phenotype of mice heterozygous (HET) or homozygous (HOM) for the disrupted Ppp2r5a allele and wild type (WT) littermates was characterized under basal conditions and following acute β-AR stimulation with dobutamine (DOB; 0.75 mg/kg i.p.) or sustained β-AR stimulation by 2-week infusion of isoproterenol (ISO; 30 mg/kg/day s.c.). Left ventricular (LV) wall thicknesses, chamber dimensions and function were assessed by echocardiography, and heart tissue collected for gravimetric, histological, and biochemical analyses. Western blot analysis revealed partial and complete loss of B56α protein in hearts from HET and HOM mice, respectively, and no changes in the expression of other PP2A regulatory, catalytic or scaffolding subunits. PP2A catalytic activity was reduced in hearts of both HET and HOM mice. There were no differences in the basal cardiac phenotype between genotypes. Acute DOB stimulation induced the expected inotropic response in WT and HET mice, which was attenuated in HOM mice. In contrast, DOB-induced increases in heart rate were unaffected by B56α deficiency. In WT mice, ISO infusion increased LV wall thicknesses, cardiomyocyte area and ventricular mass, without LV dilation, systolic dysfunction, collagen deposition or foetal gene expression. The hypertrophic response to ISO was blunted in mice deficient for B56α. Conclusion These findings identify B56α as a potential regulator of cardiac structure and function during β-AR stimulation.

Whole exome and targeted gene sequencing to detect pathogenic recessive variants in early onset cerebellar ataxia

2019 ◽  
Vol 96 (6) ◽  
pp. 566-574
Author(s):  
Sunil Shakya ◽  
Renu Kumari ◽  
Varun Suroliya ◽  
Nishu Tyagi ◽  
Aditi Joshi ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Early Onset ◽  
Gene Sequencing ◽  
Whole Exome ◽  
Targeted Gene Sequencing

Targeted Gene Sequencing Panels: Applicability for Neoantigen Profiling of Colon and Rectal Adenocarcinoma

2019 ◽  
Vol 13 (2) ◽  
pp. 146-153
Author(s):  
A. V. Kanygina ◽  
E. I. Sharova ◽  
R. I. Sultanov ◽  
Y. A. Shelygin ◽  
Y. V. Doludin ◽  
...  
Keyword(s):  
Rectal Adenocarcinoma ◽  
Gene Sequencing ◽  
Targeted Gene Sequencing

Clinical Implementation of Targeted Gene Sequencing for Malformation of Cortical Development

2020 ◽  
Vol 103 ◽  
pp. 27-34
Author(s):  
Sangbo Lee ◽  
Se Hee Kim ◽  
Borahm Kim ◽  
Seung-Tae Lee ◽  
Jong Rak Choi ◽  
...  
Keyword(s):  
Cortical Development ◽  
Gene Sequencing ◽  
Clinical Implementation ◽  
Malformation Of Cortical Development ◽  
Targeted Gene Sequencing
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