A novel homozygous missense variant in the NAXE gene in an Iranian family with progressive encephalopathy with brain edema and leukoencephalopathy

2021 ◽  
Author(s):  
Pouria Mohammadi ◽  
Morteza Heidari ◽  
Mahmoud Reza Ashrafi ◽  
Nejat Mahdieh ◽  
Masoud Garshasbi
Keyword(s):  
Brain Edema ◽  
Missense Variant ◽  
Progressive Encephalopathy ◽  
Iranian Family

A novel missense variant in GPT2 causes non-syndromic autosomal recessive intellectual disability in a consanguineous Iranian family

2020 ◽  
Vol 63 (5) ◽  
pp. 103853 ◽  
Author(s):  
Sima Binaafar ◽  
Ehsan Razmara ◽  
Nejat Mahdieh ◽  
Hamidreza Sahebjame ◽  
Ali Reza Tavasoli ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Autosomal Recessive ◽  
Missense Variant ◽  
Iranian Family

A Novel Pathogenic Variant in the CABP2 Gene Causes Severe Nonsyndromic Hearing Loss in a Consanguineous Iranian Family

2019 ◽  
Vol 24 (5) ◽  
pp. 258-263 ◽  
Author(s):  
Mahbobeh Koohiyan ◽  
Mohammad Reza Noori-Daloii ◽  
Morteza Hashemzadeh-Chaleshtori ◽  
Mansoor Salehi ◽  
Hamidreza Abtahi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Missense Variant ◽  
Pedigree Analysis ◽  
Gjb2 Gene ◽  
Genetic Linkage Analysis ◽  
Complex Process ◽  
Whole Exome ◽  
The Family ◽  
Iranian Family ◽  
Molecular Interpretation

Background and Objectives: Hereditary hearing loss (HL) can originate from mutations in one of many genes involved in the complex process of hearing. CABP2 mutations have been reported to cause moderate HL. Here, we report the whole exome sequencing (WES) of a proband presenting with prelingual, severe HL in an Iranian family. Methods: A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in the family with 2 affected members. After excluding mutations in the GJB2 gene and 7 other most common autosomal recessive nonsyndromic HL (ARNSHL) genes via Sanger sequencing and genetic linkage analysis in the family, WES was utilized to find the possible etiology of the disease. Results: WES results showed a novel rare variant (c.311G>A) in the CABP2gene.This missense variant in the exon 4 of the CABP2gene meets the criteria of being pathogenic according to the American College of Medical Genetics and Genomics (ACMG) interpretation guidelines. Conclusions: Up to now, 3 mutations have been reported for the CABP2gene to cause moderate ARNSHL in different populations. Our results show that CABP2variantsalso cause severe ARNSHL, adding CABP2to the growing list of genes that exhibit phenotypic heterogeneity. Expanding our understanding of the mutational spectrum of HL genes is an important step in providing the correct clinical molecular interpretation and diagnosis for patients.

Jansky-Bielschowsky syndrome, a lysosomal disease: First diagnosed cash in Oman

1992 ◽  
Vol 50 (1) ◽  
pp. 632-633
Author(s):  
Line Buhl ◽  
David Muirhead
Keyword(s):  
Mental Retardation ◽  
Clinical Picture ◽  
Neurological Disorder ◽  
Clinical Presentation ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Infantile Form ◽  
Lysosomal Disease ◽  
Juvenile Form ◽  
Progressive Encephalopathy ◽  
Lysosomal Diseases

There are four lysosomal diseases of which the neuronal ceroid lipofuscinosis is the rarest. The clinical presentation and their characteric abnormal ultrastructure subdivide them into four types. These are known as the Infantile form (Santavuori-Haltia), Late infantile form (Jansky-Bielschowsky), Juvenile form (Batten-Spielmeyer-Voght) and the Adult form (Kuph's).An 8 year old Omani girl presented wth myclonic jerks since the age of 4 years, with progressive encephalopathy, mental retardation, ataxia and loss of vision. An ophthalmoscopy was performed followed by rectal suction biopsies (fig. 1). A previous sibling had died of an undiagnosed neurological disorder with a similar clinical picture.

Reconsidering NMIHBA Core Features: Macrocephaly Is Not a So Unusual Sign in PRUNE1-Related Encephalopathy

2020 ◽  
Author(s):  
Roberta Battini ◽  
Enrico Bertini ◽  
Roberta Milone ◽  
Chiara Aiello ◽  
Rosa Pasquariello ◽  
...  
Keyword(s):  
Nervous System ◽  
Differential Diagnosis ◽  
Clinical Features ◽  
Neurodevelopmental Disorder ◽  
Recurrent Mutation ◽  
Clinical Suspicion ◽  
Alexander Disease ◽  
Brain Anomalies ◽  
Progressive Encephalopathy ◽  
Core Features

Abstract PRUNE1-related disorders manifest as severe neurodevelopmental conditions associated with neurodegeneration, implying a differential diagnosis at birth with static encephalopathies, and later with those manifesting progressive brain damage with the involvement of both the central and the peripheral nervous system.Here we report on another patient with PRUNE1 (p.Asp106Asn) recurrent mutation, whose leukodystrophy, inferior olives hyperintensity, and macrocephaly led to the misleading clinical suspicion of Alexander disease. Clinical features, together with other recent descriptions, suggest avoiding the term “microcephaly” in defining this disorder that could be renamed “neurodevelopmental disorder with progressive encephalopathy, hypotonia, and variable brain anomalies” (NPEHBA).

Two Different UGT1A1 Mutations causing Crigler–Najjar Syndrome types I and II in an Iranian Family

2015 ◽  
Vol 24 (4) ◽  
pp. 523-526 ◽  
Author(s):  
Yoshihiro Maruo ◽  
Mahdiyeh Behnam ◽  
Shinichi Ikushiro ◽  
Sayuri Nakahara ◽  
Narges Nouri ◽  
...  
Keyword(s):  
Serum Bilirubin ◽  
Total Serum Bilirubin ◽  
Total Serum ◽  
Compound Heterozygous ◽  
Type I ◽  
Syndrome Type ◽  
Type Ii ◽  
Wild Type ◽  
Iranian Family ◽  
Udp Glucuronosyltransferase

Background: Crigler–Najjar syndrome type I (CN-1) and type II (CN-2) are rare hereditary unconjugated hyperbilirubinemia disorders. However, there have been no reports regarding the co-existence of CN-1 and CN-2 in one family. We experienced a case of an Iranian family that included members with either CN-1 or CN-2. Genetic analysis revealed a mutation in the bilirubin UDP-glucuronosyltransferase (UGT1A1) gene that resulted in residual enzymatic activity.Case report: The female proband developed severe hyperbilirubinemia [total serum bilirubin concentration (TB) = 34.8 mg/dL] with bilirubin encephalopathy (kernicterus) and died after liver transplantation. Her family history included a cousin with kernicterus (TB = 30.0 mg/dL) diagnosed as CN-1. Her great grandfather (TB unknown) and uncle (TB = 23.0 mg/dL) developed jaundice, but without any treatment, they remained healthy as CN-2. Results: The affected cousin was homozygous for a novel frameshift mutation (c.381insGG, p.C127WfsX23). The affected uncle was compound heterozygous for p.C127WfsX23 and p.V225G linked with A(TA)7TAA. p.V225G-UGT1A1 reduced glucuronidation activity to 60% of wild-type. Thus, linkage of A(TA)7TAA and p.V225G might reduce UGT1A1 activity to 18%–36 % of the wild-type. Conclusion: Genetic and in vitro expression analyses are useful for accurate genetic counseling for a family with a history of both CN-1 and CN-2. Abbreviations: CN-1: Crigler–Najjar syndrome type I; CN-2: Crigler–Najjar syndrome type II; GS: Gilbert syndrome; UGT1A1: bilirubin UDP-glucuronosyltransferase; WT: Wild type; TB: total serum bilirubin.

Intracerebral Hematoma, Perihemorrhagic Edema and Urinary Excreted Cysteinyl Leukotrienes Correlation Study

2014 ◽  
Vol 68 (2) ◽  
pp. 85-88
Author(s):  
Natalija Dolnenec-Baneva ◽  
Dijana Nikodijevic ◽  
Gordana Kiteva-Trenchevska ◽  
Igor Petrov ◽  
Dragana Petrovska-Cvetkovska ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Correlation Study ◽  
Intracerebral Hematoma ◽  
Moderate Correlation ◽  
Hematoma Volume ◽  
Cysteinyl Leukotrienes ◽  
Edema Volume ◽  
Perihemorrhagic Edema

AbstractIntroduction.Several mechanisms in formation of perihemorrhagic edema are activated after contact of brain tissue-extravasated blood in intracerebral hemorrhage. Cysteinyl leukotrienes (cysLT) (C4, D4, E4) are included in this process as significant edema factors and they determine the neurological deficit and outcome. The study aim was a 5-day follow-up (admission/3 day/5 day) of urinary cysLT, hematoma volume, edema volume values and their correlation in patients after spontaneous, primary supratentorial intracerebral hemorrhage.Methods.An enzyme immunoassay was used for urinary cysLT measured in 62 patients and 80 healthy controls. Hematoma and edema volumes were visualized and measured by computed tomography and mathematically calculated with a special spheroid shape formula (V=AxBxC/2).Results.CysLT of hemorrhagic patients (1842.20±1413.2, 1181.54±906.2, 982.30±774.2pg/ml/mg creatinine) were significantly excreted (p<0.01). Brain edema (12.86±13.5, 22.38±21.1, 28.45±29.4cm3) was significantly increased (p<0.01). Hematoma volume values (13.05±14.5, 13.13±14.7, 12.99±14.7cm3) were not significant (p>0.05). A high correlation (multiple regression) between cysLT, hematoma and edema was found on the 3rdday (R=0.6) and a moderate correlation at admission (R=0.3) and on the 5thday (R=0.3).Conclusion.In our 5-day follow-up study a significant cysLT brain synthesis and significant brain edema progression versus constant hematoma volume values in hemorrhagic patients was found. A high correlation between cysLT, hematoma and edema volume was found on the 3rdday, a moderate correlation on admission and on the 5thday, which means that high cysLT and hematoma values were associated with high/moderate edema values.

Inhibition of microRNA-155 Alleviates Neurological Dysfunction Following Transient Global Ischemia and Contribution of Neuroinflammation and Oxidative Stress in the Hippocampus

2020 ◽  
Vol 25 (40) ◽  
pp. 4310-4317 ◽  
Author(s):  
Lichao Sun ◽  
Shouqin Ji ◽  
Jihong Xing
Keyword(s):  
Oxidative Stress ◽  
Brain Edema ◽  
Severity Score ◽  
Global Ischemia ◽  
Signal Pathways ◽  
Neurological Severity Score ◽  
Tnf Α ◽  
Transient Global Ischemia ◽  
And Oxidative Stress

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

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