MCAD deficiency caused by compound heterozygous pathogenic variants in ACADM

AbstractMedium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is an autosomal recessive disease caused by biallelic pathogenic ACADM variants. We report a case of an asymptomatic Japanese girl with MCAD deficiency caused by compound heterozygous pathogenic variants (NM_000016.5:c.1040G > T (p.Gly347Val) and c.449_452delCTGA (p.Thr150ArgfsTer4)). Because the MCAD residual activity in lymphocytes of the patient was below the limit of quantification, both variants are likely to cause complete loss of MCAD enzymatic activity.

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Genetics of alkaptonuria – an overview

Acta Facultatis Pharmaceuticae Universitatis Comenianae ◽

10.1515/afpuc-2015-0021 ◽

2015 ◽

Vol 62 (s11) ◽

pp. 27-32

Author(s):

Andrea Zatkova ◽

Martina Nemethova

Keyword(s):

Inborn Error ◽

Autosomal Recessive ◽

Autosomal Recessive Disease ◽

Homogentisic Acid ◽

Compound Heterozygous ◽

Ochronotic Arthropathy ◽

Pathogenic Variants ◽

Gene Coding ◽

Metabolic Block ◽

Rare Autosomal Recessive Disease

Abstract Alkaptonuria (AKU) is the first described inborn error of metabolism and a classical example of rare autosomal recessive disease. AKU patients carry homozygous or compound heterozygous mutations of the gene coding for enzyme homogentisate dioxygenase (HGD) involved in metabolism of tyrosine. The metabolic block in AKU causes accumulation of homogentisic acid (HGA) that, with advancing age of the patient, leads to severe and painful ochronotic arthropathy. HGD gene was mapped to chromosome 3q13.3 and is composed of 14 exons. In about 400 patients, 142 pathogenic variants were reported that are listed in HGD mutations database (http://hgddatabase.cvtisr.sk/). In this review, we summarise different aspects of AKU genetics and impact of the HGD variants on enzyme function.

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Combination of Novel c.3484G> T/p.Glu162Ter Variant in ABCB11 and c.208G> A/p.Asp70Asn Variant in ATP8B1 Are Associated with Severe Symptoms in Progressive Family Intrahepatic Cholestasis

Journal of Pediatric Genetics ◽

10.1055/s-0039-1700971 ◽

2020 ◽

Vol 09 (04) ◽

pp. 285-288

Author(s):

Mervan Bekdas ◽

Guray Can ◽

Recep Eroz ◽

Selma Erdogan Duzcu

Keyword(s):

Intrahepatic Cholestasis ◽

Autosomal Recessive ◽

Autosomal Recessive Disease ◽

Bile Secretion ◽

Peripheral Blood Sample ◽

Portal Fibrosis ◽

Traditional Treatment ◽

Pathogenic Variants ◽

Chronic Cholestasis ◽

Whole Exome

AbstractProgressive family intrahepatic cholestasis (PFIC) is an autosomal recessive disease that causes chronic cholestasis. It is associated with pathogenic variants in genes that encode proteins involved in bile secretion to canaliculus from hepatocytes. In this study, we present a 16-year-old boy who presented with severe pruritus and cholestatic jaundice. All possible infectious etiologies were negative. A liver biopsy was consistent with intrahepatic cholestasis and portal fibrosis. DNA was isolated from a peripheral blood sample, and whole exome sequencing was performed. A novel c.3484G > T/p.Glu162Ter variant in the ABCB11 gene and a c.208G> A/p.Asp70Asn variant in the ATP8B1 gene were detected. Despite traditional treatment, the patient's recurrent severe symptoms did not improve. The patient was referred for a liver transplantation. This novel c.3484G > T/p.Glu162Ter variant is associated with a severe and recurrent presentation, and the two compound variants could explain the severity of PFIC.

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First case report of medium-chain acyl-coenzyme A dehydrogenase deficiency in China

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2014-0058 ◽

2015 ◽

Vol 28 (5-6) ◽

Cited By ~ 1

Author(s):

CuiLi Liang ◽

MinYan Jiang ◽

HuiYing Sheng ◽

YanNa Cai ◽

DongYan Wu ◽

...

Keyword(s):

Case Report ◽

Inborn Error ◽

Autosomal Recessive ◽

Dehydrogenase Deficiency ◽

Coenzyme A ◽

Medium Chain ◽

First Case ◽

Mitochondrial Fatty Acid ◽

Chain Acyl ◽

Acyl Coenzyme A

AbstractMedium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is an autosomal recessive inborn error of mitochondrial fatty acid β-oxidation, caused by mutations in the

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Audiological features in Serbian patients with hearing impairment identified with c.35delG in the GJB2 gene

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh201117098d ◽

2021 ◽

pp. 98-98

Author(s):

Bojana Dobric ◽

Danijela Radivojevic ◽

Jovana Jecmenica ◽

Vassos Neocleous ◽

Pavlos Fanis ◽

...

Keyword(s):

Hearing Loss ◽

Hearing Impairment ◽

Autosomal Recessive ◽

Gjb2 Gene ◽

Compound Heterozygous ◽

Heterozygous State ◽

Phenotype Correlation ◽

Pathogenic Variants ◽

Environmental Causes ◽

35Delg Mutation

Introduction/Objective. Hearing impairment (HI) is the most common sensorineural disorder with an incidence of 1/700-1000 newborns. Variants in the GJB2 gene are the major cause of autosomal recessive nonsyndromic sensorineural hearing loss (ARNSHL). The degree of HI in patients with detected mutations in GJB2 gene ranges from mild to profound. The aim of this study was to determine possible genotype-phenotype association between audiometric characteristics and detected genotypes in ARNSHL patients from Serbia. Methods. Ninety-two patients with ARNSHL underwent genetic analysis with PCR-ARMS and sequencing of the GJB2 gene. Audiological analyses were obtained in all patients using a combination of several methods to estimate the degree of hearing loss. Results. Audiological analysis performed in the 92 probands showed moderate to profound range of hearing loss. All identified pathogenic variants accounted for 42.39% of the mutant alleles (78/184 alleles), with the c.35delG mutation being the most frequent (30.43%). Genotype-phenotype correlation in an isolated group of 37 patients bearing c.35delG in the homozygous, compound heterozygous or heterozygous state. In this group the majority of patients (30/37, 81.08%) exhibited severe to profound hearing deficit. Conclusion. Association between genotype and the degree of hearing impairment in patients analyzed in this study demonstrated that patients with bi-allelic truncating mutations i.e. c.35delG, associate with the more severe hearing loss when compared with those identified with only one affected allele. The various degrees of hearing impairment observed in heterozygous patients could be explained by the presence of an undetected second mutation or other modifier genes or environmental causes.

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A Rapid MRI Technique for the Assessment of Hepatic Steatosis in a Subject with Medium-Chain Acyl-Coenzyme A Dehydrogenase (MCAD) Deficiency

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/00005176-199808000-00019 ◽

1998 ◽

Vol 27 (2) ◽

pp. 224-227 ◽

Cited By ~ 5

Author(s):

Mark Fishbein ◽

Mark Smith ◽

B. U. K. Li

Keyword(s):

Hepatic Steatosis ◽

Coenzyme A ◽

Mcad Deficiency ◽

Medium Chain ◽

Chain Acyl ◽

Rapid Mri ◽

Acyl Coenzyme A

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L-Carnitine and exercise tolerance in medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency: A pilot study

Journal of Inherited Metabolic Disease ◽

10.1007/s10545-005-5262-5 ◽

2005 ◽

Vol 28 (2) ◽

pp. 141-152 ◽

Cited By ~ 18

Author(s):

P. J. Lee ◽

E. L. Harrison ◽

M. G. Jones ◽

S. Jones ◽

J. V. Leonard ◽

...

Keyword(s):

Pilot Study ◽

Exercise Tolerance ◽

Coenzyme A ◽

Mcad Deficiency ◽

Medium Chain ◽

Chain Acyl ◽

Acyl Coenzyme A

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The genetic basis of classical galactosaemia in Polish patients

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01869-3 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Aleksandra Jezela-Stanek ◽

Anna Bauer ◽

Katarzyna Wertheim-Tysarowska ◽

Jerzy Bal ◽

Agnieszka Magdalena Rygiel ◽

...

Keyword(s):

Autosomal Recessive ◽

Genetic Basis ◽

Dna Analysis ◽

Current Knowledge ◽

Autosomal Recessive Disorder ◽

Molecular Characteristics ◽

Compound Heterozygous ◽

Classic Galactosemia ◽

Pathogenic Variants ◽

Molecular Etiology

AbstractClassic galactosemia (OMIM #230400) is an autosomal recessive disorder caused by homozygous or compound heterozygous pathogenic variants in the galactose-1-phosphate uridylyltransferase gene (GALT; 606999) on chromosome 9p13. Its diagnosis is established by detecting elevated erythrocyte galactose-1-phosphate concentration, reduced erythrocyte galactose-1-phosphate uridylyltransferase (GALT) enzyme activity. Biallelic pathogenic variants in the GALT gene is confirmed by DNA analysis. Our paper presents molecular characteristics of 195 Polish patients diagnosed with galactosemia I, intending to expand the current knowledge of this rare disease's molecular etiology. To the best of our knowledge, the described cohort of galactosemia patients is the largest single-center cohort presented so far.

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Heterozygous VPS13A and PARK2 Mutations in a Patient with Parkinsonism and Seizures

Case Reports in Neurology ◽

10.1159/000515805 ◽

2021 ◽

pp. 341-346

Author(s):

Steven D. Mitchell ◽

Roger L. Albin ◽

William T. Dauer ◽

John L. Goudreau ◽

Christos Sidiropoulos

Keyword(s):

Autosomal Recessive ◽

Autosomal Recessive Disease ◽

Clinical Symptoms ◽

Phenotypic Diversity ◽

Phenotypic Expression ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Epistatic Interactions ◽

History Of ◽

Vacuolar Protein

Neuroacanthocytosis (NA) is a diverse group of disorders in which nervous system abnormalities co-occur with irregularly shaped red blood cells called acanthocytes. Chorea-acanthocytosis is the most common of these syndromes and is an autosomal recessive disease caused by mutations in the <i>vacuolar protein sorting 13A</i> (VPS13A) gene. We report a case of early onset parkinsonism and seizures in a 43-year-old male with a family history of NA. Neurologic examinations showed cognitive impairment and marked parkinsonian signs. MRI showed bilateral basal ganglia gliosis. He was found to have a novel heterozygous mutation in the VPS13A gene, in addition a heterozygous mutation in the PARK2 gene. His clinical picture was atypical for typical chorea-acanthocytosis (ChAc). The compound heterozygous mutations of VPS13A and PARK2 provide the most plausible explanation for this patient’s clinical symptoms. This case adds to the phenotypic diversity of ChAc. More research is needed to fully understand the roles of epistatic interactions on phenotypic expression of neurodegenerative diseases.

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Three Novel Variants of CEP290 and CC2D2DA and a Link Between ZNF77 and SHH Signaling Pathway Are Found in Two Meckel-Gruber Syndrome Fetuses

Reproductive Sciences ◽

10.1007/s43032-021-00835-5 ◽

2022 ◽

Author(s):

Zhidan Hong ◽

Xuanyi He ◽

Fang Yu ◽

Huanyu Liu ◽

Xiaoli Zhang ◽

...

Keyword(s):

Autosomal Recessive ◽

Pathological Examination ◽

Compound Heterozygous ◽

Over Expression ◽

Pathogenic Variants ◽

Whole Exome ◽

The Family ◽

Novel Variants ◽

Novel Variant ◽

Missed Diagnosis

AbstractMeckel-Gruber syndrome (MKS) is a rare lethal autosomal recessive inherited disorder. Missed diagnosis might happen in clinical works due to an unclear genotype–phenotype correlation. We analyzed two families visiting our center; the parents are normal; each of the family aborted a fetus at 12WG. Following ultrasonography and pathological examination, both were diagnosed as MKS. Whole exome sequencing identified a compound heterozygous of two novel variants of CEP290 and a heterozygous of a novel variant of CC2D2A. Frameshift mutations in ZNF77 were also detected. Western blot analyzing whole-brain tissue showed that the expression of ZNF77, CC2D2A, and CEP290 was enhanced. HEK293T transfected with over-expression wildtype/mutated ZNF77 plasmid showed that SHH was increased in wildtype ZNF77 cells, while SHH and CC2D2A were increased in mutated ZNF77 cells. Our research provided two novel pathogenic variants of CEP290 and CC2D2A and suggested that ZNF77 might promote the expression of CC2D2A and regulate the amount of SHH.

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