scholarly journals 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

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.

scholarly journals 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

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.

scholarly journals 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

2019 ◽  
Author(s):  
Sofia Thunström ◽  
Markus Axelsson
Keyword(s):  
Case Report ◽  
Peripheral Neuropathy ◽  
De Novo ◽  
Age Of Onset ◽  
De Novo Mutation ◽  
Missense Mutations ◽  
Dural Ectasia ◽  
Whole Exome ◽  
Demyelinating Peripheral Neuropathy ◽  
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. Keywords: Leukoencephalopathia, demyelinating peripheral neuropathy, dural ectasia explained, de novo mutation, the SAMD9L gene.

scholarly journals Novel PHOX2B germline mutation in childhood medulloblastoma: a case report

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Caiping Ke ◽  
Xiaoshun Shi ◽  
Allen Menglin Chen ◽  
Chaoming Li ◽  
Bifeng Jiang ◽  
...  
Keyword(s):  
Case Report ◽  
Germline Mutation ◽  
Sanger Sequencing ◽  
De Novo ◽  
Germline Mutations ◽  
Case Presentation ◽  
Second Child ◽  
Germline Variant ◽  
Whole Exome ◽  
Childhood Medulloblastoma

Abstract Background Medulloblastoma is an aggressive brain tumor mostly found in children, few studies on pathogenic germline mutations predisposing this disease was reported. Case presentation We present an 11-year-old male with medulloblastoma, who harbors a de novo PHOX2B germline mutation as detected by whole exome sequencing (WES). Family history was negative. Sanger sequencing confirmed this mutation in peripheral blood, hair bulbs, urine and saliva. Identification of novel germline mutations is beneficial for childhood cancer screening. Conclusions This case revealed a de novo PHOX2B germline mutation as a potential cause of medulloblastoma in a child and suggests familial germline variant screening is useful when an affected family is considering having a second child.

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

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.

De Novo Development of a Cavernous Malformation of the Brain: Significance of Factors with Paracrine and Endocrine Activity: Case Report

Neurosurgery ◽  
2002 ◽  
Vol 50 (3) ◽  
pp. 646-650 ◽  
Author(s):  
Wolf Lüdemann ◽  
Verena Ellerkamp ◽  
Alexandru C. Stan ◽  
Sami Hussein
Keyword(s):  
Case Report ◽  
De Novo ◽  
Cavernous Malformation ◽  
Endocrine Activity ◽  
The Brain

scholarly journals 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 

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lichun Xie ◽  
Zhihao Xing ◽  
Changgang Li ◽  
Si-xi Liu ◽  
Fei-qiu Wen
Keyword(s):  
De Novo ◽  
Hereditary Spherocytosis ◽  
Case Reports ◽  
De Novo Mutation ◽  
Case Presentation ◽  
Important Means ◽  
Genetic Detection ◽  
Membrane Defects ◽  
Severe Jaundice ◽  
Neonates And Infants

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.

An intronic variant disrupts mRNA splicing and causes FGFR3-related skeletal dysplasia

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ting Xu ◽  
Liang Shi ◽  
Weiqian Dai ◽  
Xuefan Gu ◽  
Yongguo Yu ◽  
...  
Keyword(s):  
De Novo ◽  
Clinical Findings ◽  
Recurrent Mutation ◽  
Mrna Splicing ◽  
Additional Patient ◽  
Missense Mutations ◽  
Splicing Variant ◽  
Amino Acid Insertion ◽  
Whole Exome ◽  
Minigene Assay

Abstract Objectives Achondroplasia and hypochondroplasia are the most common forms of disproportionate short stature, of which the vast majority of cases can be attributed to the hotspot missense mutations in the gene FGFR3. Here we presented cases with a novel cryptic splicing variant of FGFR3 gene and aimed to interrogate the variant pathogenicity. Case presentaiton In whole exome sequencing of two patients with hypochondroplasia-like features, a de novo intronic variant c.1075 + 95C>G was identified, predicted to alter mRNA splicing. Minigene assay showed that this intronic variant caused retention of a 90-nucleotide segment of intron 8 in mRNA, resulting in a 30-amino acid insertion at the extracellular domain of the protein. This is the first likely pathogenic splicing variant identified in the FGFR3 gene and was detected in one additional patient among 26 genetically unresolved patients. Conclustions Our results strongly suggest that c.1075 + 95C>G is a recurrent mutation and should be included in genetic testing of FGFR3 especially for those patients with equivocal clinical findings and no exonic mutations identified.

scholarly journals A de novo variant in CASK gene causing intellectual disability and brain hypoplasia: A Case Report and Literature Review

2021 ◽  
Author(s):  
Ying Zhang ◽  
Yanyan Nie ◽  
Yu Mu ◽  
Jie Zheng ◽  
Xiaowei Xu ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mental Disorders ◽  
De Novo ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
De Novo Mutation ◽  
Loss Of Function ◽  
Bioinformatics Analyses ◽  
Whole Exome ◽  
De Novo Variant

Abstract Background：The pathogenic variation of CASK gene can cause CASK related mental disorders. The main clinical manifestations are microcephaly with pontine and cerebellar hypoplasia, X-linked mental disorders with or without nystagmus and FG syndrome. The main pathogenic mechanism is the loss of function of related protein caused by mutation. We reported a Chinese male newborn with a de novo variant in CASK gene. Case presentation：We present an 18-day-old baby with intellectual disability and brain hypoplasia. Whole-exome sequencing was performed, which detected a hemizygous missense mutation c.764G>A of CASK gene. The mutation changed the 255th amino acid from Arg to His. Software based bioinformatics analyses were conducted to infer its functional effect.Conclusions：In this paper, a de novo mutation of CASK gene was reported. Moreover, a detailed description of all the cases described in the literature is reported.CASK mutations cause a variety of clinical phenotypes. Its diagnosis is difficult due to the lack of typical clinical symptoms. Genetic testing should be performed as early as possible if this disease is suspected. This case provides an important reference for the diagnosis and treatment of future cases.

scholarly journals Catatonia Associated With Late Paraphrenia Successfully Treated With Lithium: A Case Report

2020 ◽  
Author(s):  
Hiroko Sugawara ◽  
Junpei Takamatsu ◽  
Mamoru Hashimoto ◽  
Manabu Ikeda
Keyword(s):  
Case Report ◽  
Mood Disorders ◽  
Electroconvulsive Therapy ◽  
Late Onset ◽  
Treatment Strategies ◽  
Psychotic Symptoms ◽  
Case Presentation ◽  
Limited Efficacy ◽  
Cumulative Evidence ◽  
The Brain

Abstract Background: Catatonia is a psychomotor syndrome that presents various symptoms ranging from stupor to agitation, with prominent disturbances of volition. Its pathogenesis is poorly understood. Benzodiazepines and electroconvulsive therapy (ECT) are safe and effective standard treatments for catatonia; however, alternative treatment strategies have not been established in cases where these treatments are either ineffective or unavailable. Here, we report a case of catatonia associated with late paraphrenia classified as very-late-onset schizophrenia-like psychosis, which was successfully treated with lithium. Case presentation: A 66-year-old single man with hearing impairment developed hallucination and delusions and presented with catatonic stupor after a fall. He initially responded to benzodiazepine therapy; however, his psychotic symptoms became clinically evident and benzodiazepine provided limited efficacy. Blonanserin was ineffective, and ECT was unavailable. His catatonic and psychotic symptoms were finally relieved by lithium monotherapy.Conclusions: Catatonic symptoms are common in patients with mood disorders, suggesting that lithium may be effective in these cases. Moreover, lithium may be effective for both catatonic and psychotic symptoms, as it normalizes imbalances of excitatory and inhibitory systems in the brain, which underlies major psychosis. Cumulative evidence from further cases is needed to validate our findings.

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