Identification of a De Novoc.1000delA ANK1 mutation associated to hereditary spherocytosis in a neonate with Coombs-negative hemolytic jaundice-case reports and review of the literature

Abstract Background To strengthen the understanding of Hereditary Spherocytosis (HS) and determine the disease-causing mutation present with neonatal jaundice. HS is a hemolytic condition resulting from various erythrocyte membrane defects. Many different mutations result in HS, including mutations in ANK1. Case presentation A term neonate presented at ten hours with severe jaundice requiring exchange transfusion. At two months he was hospitalized due to repeated pallor and anemia requiring blood transfusions. Using next-generation sequencing, we discovered the responsible mutation in the proband but not in his parents; a heterozygous nucleotide variation of c.1000delA (p.1334Sfs*6) in ANK1. Thus hereditary spherocytosis was diagnosed. Conclusions Genetic detection is an important means of discovering the cause of hemolytic anemia in neonates and infants where routine diagnostic tests are unrevealing. We found a novel de novo mutation, c.1000delA (p.1334Sfs*6) in ANK1 that might account for other cases of HS in the Chinese population.

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Band 3Tambau: a de novo mutation in the AE1 gene associated with hereditary spherocytosis. Implications for anion exchange and insertion into the red blood cell membrane

European Journal Of Haematology ◽

10.1111/j.1600-0609.2004.00405.x ◽

2005 ◽

Vol 74 (5) ◽

pp. 396-401 ◽

Cited By ~ 8

Author(s):

Paulo Roberto Moura Lima ◽

Mariana Ozello Baratti ◽

Maria Lucia Chiattone ◽

Fernando Ferreira Costa ◽

Sara Teresinha Olalla Saad

Keyword(s):

Cell Membrane ◽

Blood Cell ◽

Anion Exchange ◽

Red Blood Cell ◽

De Novo ◽

Hereditary Spherocytosis ◽

De Novo Mutation ◽

Red Blood Cell Membrane

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Report on 2 Liver Damage Cases of Unknown Reason with ANK1 Mutations

10.21203/rs.3.rs-126667/v1 ◽

2020 ◽

Author(s):

Lianhu Yu ◽

Yongmei Xiao ◽

Yizhong Wang ◽

Dan Li ◽

Ting Zhang

Keyword(s):

Liver Biopsy ◽

Iron Overload ◽

Liver Damage ◽

Alanine Aminotransferase ◽

Iron Homeostasis ◽

De Novo ◽

Hereditary Spherocytosis ◽

Blue Staining ◽

Case Presentation ◽

Unknown Reason

Abstract Background: ANK1 mutations are usually related to hereditary spherocytosis. Few studies show direct relationships between ANK1 mutations and liver damage. Recent researches revealed that ANK1 mutations may downregulate the expression of hepcidin, a key hepatic hormone important to iron homeostasis. Hepcidin deficiency can induce iron overload that do harm to liver cells and cause ferroptosis.Case Presentation: In both cases, yellowing of skin and hepatomegaly were found. Lab results showed increased alanine aminotransferase (ALT) and aspartate aminotransferases (AST). Genetic tests confirmed de novo heterozygous mutations in ANK1 gene. Liver biopsy of one child indicated mild liver damage. Prussian blue staining revealed iron accumulation. Conclusions: Here we report 2 cases featuring ANK1 mutations with liver damage of unidentified causes. We suspect that ANK1 mutation is related to liver damage through decreasing hepcidin, which may cause iron overload and then ferroptosis.

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Leukoencephalopathia, demyelinating peripheral neuropathy and dural ectasia explained by a not formerly described de novo mutation in the SAMD9L gene, ends 27 years of investigations – A case report

10.21203/rs.2.307/v2 ◽

2019 ◽

Author(s):

Sofia Thunström ◽

Markus Axelsson

Keyword(s):

Case Report ◽

De Novo ◽

Age Of Onset ◽

De Novo Mutation ◽

Missense Mutations ◽

Case Presentation ◽

Whole Exome ◽

Demyelinating Peripheral Neuropathy ◽

The Brain ◽

Multiple Cysts

Abstract Background: Missense mutations in SAMD9L gene is associated with ataxia-pancytopenia syndrome (ATXPC), OMIM#159550. Common clinical features in these patients include neurological and hematological symptoms. The phenotype and age of onset is variable. Case presentation: In this case report whole exome sequencing (WES) revealed a not previously reported de novo variant c.2686T>G, p.(Phe896Val) in SAMD9L in a patient with widespread findings of slow developing pathology in the peripheral and central nervous system. The clinical picture was dominated by neurological symptoms, unlike previously described cases, and in addition dural ectasias and multiple cysts in the brain was observed using magnetic resonance imaging. Conclusions: This case underscores the effect of variable expressivity, i.e. different mutations in the same gene can cause different phenotypes.

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Leukoencephalopathia, demyelinating peripheral neuropathy and dural ectasia explained by a not formerly described de novo mutation in the SAMD9L gene, ends 27 years of investigations – A case report

10.21203/rs.2.307/v3 ◽

2019 ◽

Author(s):

Sofia Thunström ◽

Markus Axelsson

Keyword(s):

Case Report ◽

De Novo ◽

Age Of Onset ◽

De Novo Mutation ◽

Missense Mutations ◽

Case Presentation ◽

Whole Exome ◽

Demyelinating Peripheral Neuropathy ◽

The Brain ◽

Multiple Cysts

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Direct Transmission of Within-Host Mycobacterium Tuberculosis Diversity to Secondary Cases Can Lead to Variable Between-Host Heterogeneity Without De Novo Mutation: A Genomic Investigation

SSRN Electronic Journal ◽

10.2139/ssrn.3384856 ◽

2019 ◽

Author(s):

Marie Séraphin ◽

Anders Norman ◽

Erik Michael Rasmussen ◽

Alexandra M. Gerace ◽

Calin Chiribau ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

De Novo ◽

De Novo Mutation ◽

Direct Transmission ◽

Host Heterogeneity

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Spontaneous haemorrhage of an adrenal angiomyolipoma: case report

African Journal of Urology ◽

10.1186/s12301-019-0006-1 ◽

2019 ◽

Vol 25 (1) ◽

Author(s):

Danielle Whiting ◽

Ian Rudd ◽

Amit Goel ◽

Seshadri Sriprasad ◽

Sanjeev Madaan

Keyword(s):

Case Reports ◽

Case Presentation ◽

Open Adrenalectomy ◽

Large Size ◽

History Of ◽

Loin Pain ◽

Benign Tumours ◽

Spontaneous Haemorrhage ◽

Mesenchymal Tumours

Abstract Background Angiomyolipomas are rare mesenchymal tumours arising from the perivascular epithelioid cells consisting of variable amounts of adipose, thick-walled blood vessels and smooth muscle cells. These benign tumours commonly occur in the kidney with only a few case reports of adrenal angiomyolipomas which have the potential to reach a large size and haemorrhage. Case presentation A 45-year-old lady presented with a 3-week history of right loin pain, nausea and vomiting. A CT scan revealed a right adrenal angiomyolipoma measuring 6.3 × 6.8 cm with associated haemorrhage. The lesion was successfully treated with right open adrenalectomy, and histology confirmed the diagnosis of adrenal angiomyolipoma. The patient remained well with no evidence of recurrence at the 36-month follow-up. Conclusion Adrenal angiomyolipomas are rare benign tumours that have the ability to reach a large size and potential to bleed. Here, we report the second case of spontaneous haemorrhage in an adrenal angiomyolipoma, which was successfully treated with open adrenalectomy.

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Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder

Molecular Brain ◽

10.1186/s13041-021-00769-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Kohei Kitagawa ◽

Kensuke Matsumura ◽

Masayuki Baba ◽

Momoka Kondo ◽

Tomoya Takemoto ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Social Behavior ◽

Mouse Model ◽

Mouse Models ◽

De Novo ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

De Novo Mutation ◽

Behavioral Deficits

AbstractAutism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.

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The L1-dependant and Pol III transcribed Alu retrotransposon, from its discovery to innate immunity

Molecular Biology Reports ◽

10.1007/s11033-021-06258-4 ◽

2021 ◽

Vol 48 (3) ◽

pp. 2775-2789

Author(s):

Ludwig Stenz

Keyword(s):

Human Genome ◽

Viral Infections ◽

De Novo ◽

Current Knowledge ◽

Innate Immune ◽

De Novo Mutation ◽

Neuronal Diversity ◽

Alu Sequences ◽

Pol Iii ◽

The Brain

AbstractThe 300 bp dimeric repeats digestible by AluI were discovered in 1979. Since then, Alu were involved in the most fundamental epigenetic mechanisms, namely reprogramming, pluripotency, imprinting and mosaicism. These Alu encode a family of retrotransposons transcribed by the RNA Pol III machinery, notably when the cytosines that constitute their sequences are de-methylated. Then, Alu hijack the functions of ORF2 encoded by another transposons named L1 during reverse transcription and integration into new sites. That mechanism functions as a complex genetic parasite able to copy-paste Alu sequences. Doing that, Alu have modified even the size of the human genome, as well as of other primate genomes, during 65 million years of co-evolution. Actually, one germline retro-transposition still occurs each 20 births. Thus, Alu continue to modify our human genome nowadays and were implicated in de novo mutation causing diseases including deletions, duplications and rearrangements. Most recently, retrotransposons were found to trigger neuronal diversity by inducing mosaicism in the brain. Finally, boosted during viral infections, Alu clearly interact with the innate immune system. The purpose of that review is to give a condensed overview of all these major findings that concern the fascinating physiology of Alu from their discovery up to the current knowledge.

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Clozapine-induced stuttering in the absence of known risk factors: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-021-02803-8 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Florence Jaguga

Keyword(s):

Risk Factors ◽

Family History ◽

Side Effect ◽

Case Reports ◽

Extrapyramidal Symptoms ◽

Prior History ◽

Case Presentation ◽

Rare Side Effect ◽

History Of ◽

Electrophysiological Findings

Abstract Background Stuttering is a rare side effect of clozapine. It has been shown to occur in the presence of one or more factors such as abnormal electrophysiological findings and seizures, extrapyramidal symptoms, brain pathology, and a family history of stuttering. Few case reports have documented the occurrence of clozapine-induced stuttering in the absence of these risk factors. Case presentation A 29-year-old African male on clozapine for treatment-resistant schizophrenia presented with stuttering at a dosage of 400 mg/day that resolved with dose reduction. Electroencephalogram findings were normal, and there was no clinical evidence of seizures. The patient had no prior history or family history of stuttering, had a normal neurological examination, and showed no signs of extrapyramidal symptoms. Conclusion Clinicians ought to be aware of stuttering as a side effect of clozapine, even in the absence of known risk factors. Further research should investigate the pathophysiology of clozapine-induced stuttering.

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