Autozygosity mapping of methylmalonic acidemia associated genes by short tandem repeat markers facilitates the identification of five novel mutations in an Iranian patient cohort.

Abstract:

:Isolated Methylmalonic acidemia/aciduria (MMA) is a group of inborn errors of metabolism disease which is caused by defect in methylmalonyl-CoA mutase (MCM) enzyme. The enzyme has a key function in the catabolism of branched chain amino acids (BCAA, isoleucine, and valine), methionine, and threonine. MCM is encoded by a single gene named "MUT". Other subtypes of MMA are caused by mutations in cblA (encoded by MMAA) and cblB (encoded by MMAB), which is involved in the synthesis of methylmalonyl-coenzyme A cofactor. Different types of mutations have been identified as the cause of MMA. However, the mutation spectrum of MMA in Iran has not been studied so far. Here, we aimed to investigate the MMA causative mutations in the Iranian population. Using STR (Short Tandem Repeat) markers, we performed autozygosity mapping to identify the potential pathogenic variants in 11 patients with clinical diagnosis of MMA. Nineteen STR markers which are linked to the MUT, MMAA and MMAB genes (the genes with known causative mutations in MMA) were selected for PCR-amplification using two recently designed multiplex PCR panels. Next, the families that were diagnosed with homozygous haplotypes for the candidate genes were directly sequenced. Five novel mutations (c.805delG, c.693delC, c.223A > T, c.668A > G and c.976A > G in MUT) were identified beside other 4 recurrent mutations (c.361insT in MUT, c.571C > T and c.197-1 G > T in MMAB and c.1075C > T in MMAA). In silico analyses were also performed to predict the pathogenicity of the identified variants. The mutation c.571C > T in MMAB was the most common mutation in our study.

journal_name

Metab Brain Dis

journal_title

Metabolic brain disease

authors

Shafaat M,Alaee MR,Rahmanifar A,Setoodeh A,Razzaghy-Azar M,Bagherian H,Bagheri SD,Zafarghandi Motlagh F,Hashemi M,Abiri M,Zeinali S

doi

10.1007/s11011-018-0277-4

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

1689-1697

issue

5

eissn

0885-7490

issn

1573-7365

pii

10.1007/s11011-018-0277-4

journal_volume

33

pub_type

杂志文章
  • The 13C isotope and nuclear magnetic resonance: unique tools for the study of brain metabolism.

    abstract::As studies of brain metabolism grow in complexity, investigators turn increasingly to nuclear magnetic resonance spectroscopy combined with 13C isotopic labeling. The unique ability to detect labeling non-destructively in specific carbon positions of individual compounds has opened the way to investigate brain metabol...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章,评审

    doi:10.1007/BF02029492

    authors: Mason GF,Behar KL,Lai JC

    更新日期:1996-12-01 00:00:00

  • Aberrant interhemispheric functional coordination in patients with HBV-related cirrhosis and minimal hepatic encephalopathy.

    abstract::Aberrant brain functional connectivity has been considered as the important mechanism underlying minimal hepatic encephalopathy (MHE); however, little is known about the change in interhemispheric connection in MHE patients. Twenty patients with HBV-related cirrhosis and MHE and 15 healthy controls were included in th...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-014-9505-8

    authors: Chen HJ,Wang Y,Yang M,Zhu XQ,Teng GJ

    更新日期:2014-09-01 00:00:00

  • The serum zinc concentration as a potential biological marker in patients with major depressive disorder.

    abstract::Despite many clinical trials assessing the role of zinc in major depressive disorder (MDD), the conclusions still remain ambiguous. The aim of the present clinical study was to determine and comparison the zinc concentration in the blood of MDD patients (active stage or remission) and healthy volunteers (controls), as...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-016-9888-9

    authors: Styczeń K,Sowa-Kućma M,Siwek M,Dudek D,Reczyński W,Szewczyk B,Misztak P,Topór-Mądry R,Opoka W,Nowak G

    更新日期:2017-02-01 00:00:00

  • Effects of fulminant hepatic encephalopathy on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na(+),K (+))- and Mg (2+)-ATPase: comparison of the enzymes' response to in vitro treatment with ammonia.

    abstract::Hepatic encephalopathy can be a life-threatening complication of fulminant hepatic failure. By understanding the pathophysiology involved in the induction of this neuropsychiatric disorder, future therapeutic and/or preventive attempts could be considered. In this study, an attempt has been made in order to shed more ...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-008-9091-8

    authors: Zarros A,Theocharis S,Skandali N,Tsakiris S

    更新日期:2008-09-01 00:00:00

  • Erp72 expression activated by transient cerebral ischemia or disturbance of neuronal endoplasmic reticulum calcium stores.

    abstract::Stress-induced activation of the expression of the endoplasmic reticulum (ER)-resident chaperon and member of the protein disulfide isomerase family erp72 was studied after transient cerebral ischemia in vivo using the four-vessel occlusion method and experimental depletion of ER calcium stores in primary neuronal cel...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1023/a:1020631029168

    authors: Paschen W,Gissel C,Linden T,Doutheil J

    更新日期:1998-03-01 00:00:00

  • Effects of 1,4-butanediol administration on oxidative stress in rat brain: study of the neurotoxicity of gamma-hydroxybutyric acid in vivo.

    abstract::gamma-Hydroxybutyric acid (GHB) is a naturally occurring compound in the central nervous system (CNS) whose tissue concentration are highly increased in the neurometabolic-inherited deficiency of succinic semialdehyde dehydrogenase (SSADH) activity or due to intoxication. SSADH deficiency is biochemically characterize...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-009-9136-7

    authors: Sgaravatti AM,Magnusson AS,Oliveira AS,Mescka CP,Zanin F,Sgarbi MB,Pederzolli CD,Wyse AT,Wannmacher CM,Wajner M,Dutra-Filho CS

    更新日期:2009-06-01 00:00:00

  • Anxiolytic-like effects of α-asarone in a mouse model of chronic pain.

    abstract::α-asarone (ASR) is a major bioactive compound isolated from the rhizome of Acorus tatarinowii Schott and it has extensive biological effects. Clinically, anxiety disorder is a common comorbidity of chronic pain. However, limited information is available regarding the effects of ASR on chronic pain-related anxiety. Thi...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-017-0108-z

    authors: Tian J,Tian Z,Qin SL,Zhao PY,Jiang X,Tian Z

    更新日期:2017-12-01 00:00:00

  • Effect of blood ammonia elevation following oral glutamine load on the psychometric performance of cirrhotic patients.

    abstract::Oral glutamine challenge is a method to increase blood ammonia and may be used to study the ammonia lowering effect of drugs potentially useful in hepatic encephalopathy (HE). We tested its influence on the psychometric performance of 18 cirrhotic patients without HE. Twelve nonencephalopatic cirrhotic patients were s...

    journal_title:Metabolic brain disease

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1021926601907

    authors: Masini A,Efrati C,Merli M,Nicolao F,Amodio P,Del Piccolo F,Riggio O

    更新日期:2003-03-01 00:00:00

  • Evidence of a vicious cycle in glutamine synthesis and breakdown in pathogenesis of hepatic encephalopathy-therapeutic perspectives.

    abstract::There is substantial clinical and experimental evidence that ammonia is a major factor in the pathogenesis of hepatic encephalopathy. In the article is demonstrated that in hepatocellular dysfunction, ammonia detoxification to glutamine (GLN) in skeletal muscle, brain, and likely the lungs, is activated. In addition t...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章,评审

    doi:10.1007/s11011-013-9428-9

    authors: Holecek M

    更新日期:2014-03-01 00:00:00

  • Atorvastatin ameliorates cognitive impairment, Aβ1-42 production and Tau hyperphosphorylation in APP/PS1 transgenic mice.

    abstract::Amyloid-beta (Aβ) interacts with the serine/threonine protein kinase AKT (also known as protein kinase B)/glycogen synthase kinase 3β (GSK3β) pathway and deactivates GSK3β signaling, which result in microtubule protein tau phosphorylation. Atorvastatin, a HMG-CoA reductase inhibitor, has been proven to improve learnin...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-016-9803-4

    authors: Zhou D,Liu H,Li C,Wang F,Shi Y,Liu L,Zhao X,Liu A,Zhang J,Wang C,Chen Z

    更新日期:2016-06-01 00:00:00

  • Risperidone-induced metabolic dysfunction is attenuated by Curcuma longa extract administration in mice.

    abstract::Antipsychotics, such as risperidone, increase food intake and induce alteration in glucose and lipid metabolism concomitantly with overweight and body fat increase, these biological abnormalities belong to the metabolic syndrome definition (high visceral adiposity, hypertriglyceridemia, hyperglycemia, low HDL-choleste...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-017-0133-y

    authors: Auger F,Martin F,Pétrault O,Samaillie J,Hennebelle T,Trabelsi MS,Bailleul F,Staels B,Bordet R,Duriez P

    更新日期:2018-02-01 00:00:00

  • Elevated levels of serum cholesterol are associated with better performance on tasks of episodic memory.

    abstract::We examined how serum cholesterol, an established risk factor for cerebrovascular disease (CVD), relates to cognitive function in healthy middle-older aged individuals with no neurologic or CVD history. A complete lipid panel was obtained from a cohort of one hundred twenty individuals, ages 43-85, who also underwent ...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-016-9797-y

    authors: Leritz EC,McGlinchey RE,Salat DH,Milberg WP

    更新日期:2016-04-01 00:00:00

  • Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.

    abstract::Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we exa...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-016-9816-z

    authors: Kartal Ö,Aydınöz S,Kartal AT,Kelestemur T,Caglayan AB,Beker MC,Karademir F,Süleymanoğlu S,Kul M,Yulug B,Kilic E

    更新日期:2016-08-01 00:00:00

  • Pretreatment with vitamins E and C prevent the impairment of memory caused by homocysteine administration in rats.

    abstract::Homocystinuria is a metabolic disorder caused by deficiency of cystathione beta-synthase activity leading to tissue accumulation of homocysteine (Hcy); affected patients present neurological dysfunction. Considering that Hcy induces free radical formation and that memory is impaired by oxidative stress, in the present...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1023/a:1019982223034

    authors: Reis EA,Zugno AI,Franzon R,Tagliari B,Matté C,Lammers ML,Netto CA,Wyse AT

    更新日期:2002-09-01 00:00:00

  • Induction of Rabies Virus Infection in Mice Brain may Up and Down Regulate Type II Interferon gamma via epigenetic modifications.

    abstract::As feared and deadly human diseases globally, Rabies virus contrived mechanisms to escape early immune recognition via suppression of the interferon response. This study, preliminarily investigated whether Rabies virus employs epigenetic mechanism for the suppression of the interferon using the Challenge virus standar...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-020-00553-y

    authors: Abdulazeez M,Kia GSN,Abarshi MM,Muhammad A,Ojedapo CE,Atawodi JC,Dantong D,Kwaga JKP

    更新日期:2020-06-01 00:00:00

  • Synergistic antidepressant-like effect of ferulic acid in combination with piperine: involvement of monoaminergic system.

    abstract::The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-015-9704-y

    authors: Li G,Ruan L,Chen R,Wang R,Xie X,Zhang M,Chen L,Yan Q,Reed M,Chen J,Xu Y,Pan J,Huang W

    更新日期:2015-12-01 00:00:00

  • The cholinergic neuronal phenotype in Alzheimer's disease.

    abstract::The synthesis, storage and release of acetylcholine (ACh) requires the expression of several specialized proteins, including choline acetyltransferase (ChAT) and the vesicular ACh transporter (VAChT). The VAChT gene is located within the first intron of the ChAT gene. This unique genomic organization permits coordinat...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章,评审

    doi:10.1007/BF02680013

    authors: Blusztajn JK,Berse B

    更新日期:2000-03-01 00:00:00

  • Psychopharmacology of maternal separation anxiety in vervet monkeys.

    abstract::Maternal separation in non-human primates has been proposed as a model of early adversity. The symptoms of separation anxiety were studied in vervet monkeys, during the weaning period, when psychotropic medications were administered. The control group received a normal diet and treatment groups received citalopram, re...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-006-9011-8

    authors: Marais L,Daniels W,Brand L,Viljoen F,Hugo C,Stein DJ

    更新日期:2006-09-01 00:00:00

  • Measurement of the expiratory ammonia concentration and its clinical significance.

    abstract::Although gaseous ammonia (NH3) can freely enter cells through the plasma membrane where NH3 is cyto(neuro)toxic, NH3 and ionic ammonia (NH4+) contents have not been studied in biological materials. We developed a new method for measurement of expiratory NH3 concentration, which may reflect blood NH3 concentrations. Th...

    journal_title:Metabolic brain disease

    pub_type: 临床试验,杂志文章

    doi:

    authors: Wakabayashi H,Kuwabara Y,Murata H,Kobashi K,Watanabe A

    更新日期:1997-06-01 00:00:00

  • A patient with mitochondrial disorder due to a novel mutation in MRPS22.

    abstract::MRPS22 gene defect is a very rare newly discovered mitochondrial disorder. We report a 4-month-old severely affected male infant with MRPS22 mutation. Whole exome sequencing revealed a novel homozygous splicing mutation c.339 + 5 G > A in MRPS22 gene. He has mild dysmorphism, hypotonia, developmental delay but not hyp...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-017-0074-5

    authors: Kılıç M,Oğuz KK,Kılıç E,Yüksel D,Demirci H,Sağıroğlu MŞ,Yücel-Yılmaz D,Özgül RK

    更新日期:2017-10-01 00:00:00

  • High mobility group box 1 enhances hyperthermia-induced seizures and secondary epilepsy associated with prolonged hyperthermia-induced seizures in developing rats.

    abstract::Levels of high mobility group box 1 (HMGB1), an important inflammatory mediator, are high in the serum of febrile seizure (FS) patients. However, its roles in FS and secondary epilepsy after prolonged FS are poorly understood. We demonstrate HMGB1's role in the pathogenesis of hyperthermia-induced seizures (HS) and se...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-017-0103-4

    authors: Ito M,Takahashi H,Yano H,Shimizu YI,Yano Y,Ishizaki Y,Tanaka J,Ishii E,Fukuda M

    更新日期:2017-12-01 00:00:00

  • Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1 mouse.

    abstract::Niemann-Pick type C 1 (NPC1) disease is an autosomal recessive cholesterol transport defect resulting in a neurodegenerative process in patients mainly at an early age, although some patients may start with manifestation in adult. Since loss of myelin is considered as a main pathogenetic factor, the precise mechanism ...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-011-9263-9

    authors: Yan X,Lukas J,Witt M,Wree A,Hübner R,Frech M,Köhling R,Rolfs A,Luo J

    更新日期:2011-12-01 00:00:00

  • Near infrared radiation rescues mitochondrial dysfunction in cortical neurons after oxygen-glucose deprivation.

    abstract::Near infrared radiation (NIR) is known to penetrate and affect biological systems in multiple ways. Recently, a series of experimental studies suggested that low intensity NIR may protect neuronal cells against a wide range of insults that mimic diseases such as stroke, brain trauma and neurodegeneration. However, the...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-014-9515-6

    authors: Yu Z,Liu N,Zhao J,Li Y,McCarthy TJ,Tedford CE,Lo EH,Wang X

    更新日期:2015-04-01 00:00:00

  • Acute and long-term effects of intracerebroventricular administration of α-ketoisocaproic acid on oxidative stress parameters and cognitive and noncognitive behaviors.

    abstract::Maple Syrup Urine Disease (MSUD) is biochemically characterized by elevated levels of leucine, isoleucine and valine, as well as their corresponding transaminated branched-chain α-keto acids in tissue and biological fluids. Neurological symptoms and cerebral abnormalities, whose mechanisms are still unknown, are typic...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-017-0035-z

    authors: Taschetto L,Scaini G,Zapelini HG,Ramos ÂC,Strapazzon G,Andrade VM,Réus GZ,Michels M,Dal-Pizzol F,Quevedo J,Schuck PF,Ferreira GC,Streck EL

    更新日期:2017-10-01 00:00:00

  • Acetyl-L-carnitine in hepatic encephalopathy.

    abstract::Hepatic encephalopathy is a common complication of hepatic cirrhosis. The clinical diagnosis is based on two concurrent types of symptoms: impaired mental status and impaired neuromotor function. Impaired mental status is characterized by deterioration in mental status with psychomotor dysfunction, impaired memory, an...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章,评审

    doi:10.1007/s11011-013-9376-4

    authors: Malaguarnera M

    更新日期:2013-06-01 00:00:00

  • Rivastigmine reverses cognitive deficit and acetylcholinesterase activity induced by ketamine in an animal model of schizophrenia.

    abstract::Schizophrenia is one of the most disabling mental disorders that affects up to 1 % of the population worldwide. Although the causes of this disorder remain unknown, it has been extensively characterized by a broad range of emotional, ideational and cognitive impairments. Studies indicate that schizophrenia affects neu...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-013-9417-z

    authors: Zugno AI,Julião RF,Budni J,Volpato AM,Fraga DB,Pacheco FD,Deroza PF,Luca RD,de Oliveira MB,Heylmann AS,Quevedo J

    更新日期:2013-09-01 00:00:00

  • Effects of chronic administration of fenproporex on cognitive and non-cognitive behaviors.

    abstract::Fenproporex (Fen) is an amphetamine-based anorectic; amphetamine use causes a broad range of severe cognitive deficits and anxiogenic-like effects. In this study we evaluated pharmacological effects of the chronic administration of Fen on cognitive and non-cognitive behaviors. Male adult Wistar rats received intraperi...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-014-9617-1

    authors: Gonçalves CL,Furlanetto CB,Valvassori SS,Bavaresco DV,Varela RB,Budni J,Quevedo J,Streck EL

    更新日期:2015-04-01 00:00:00

  • Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility.

    abstract::Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3 years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzym...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章,meta分析,评审

    doi:10.1007/s11011-016-9815-0

    authors: Rai V

    更新日期:2016-08-01 00:00:00

  • EGb761 improves the cognitive function of elderly db/db-/- diabetic mice by regulating the beclin-1 and NF-κB signaling pathways.

    abstract::To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db-/- mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db-/- control, db/db-/- 50 mg, db/db-/- 100 mg, wi...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-018-0295-2

    authors: Guan ZF,Zhang XM,Tao YH,Zhang Y,Huang YY,Chen G,Tang WJ,Ji G,Guo QL,Liu M,Zhang Q,Wang NN,Yu ZY,Hao-Yang,Wu GF,Tang ZP,Du ZG,Shang XL,Liu YC,Mei GH,Guo JC,Zhou HG

    更新日期:2018-12-01 00:00:00

  • Bipolar limbic expression of auto-immune thyroid targets: thyroglobulin and thyroid-stimulating hormone receptor.

    abstract::The associations between thyroid auto-immunity and neuro-psychiatric disorders are well-documented. However, there exists limited literature specifically linking auto-immune thyroid disease (AITD) to bipolar disorder (BD). Thus, we investigated the likely association between Hashimoto's disease and BD through the extr...

    journal_title:Metabolic brain disease

    pub_type: 杂志文章

    doi:10.1007/s11011-019-00437-w

    authors: Naicker M,Abbai N,Naidoo S

    更新日期:2019-10-01 00:00:00