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 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 Case Report: A Novel de novo Mutation in DNM1L Presenting With Developmental Delay, Ataxia, and Peripheral Neuropathy

2021 ◽  
Vol 9 ◽  
Author(s):  
Yanping Wei ◽  
Min Qian
Keyword(s):  
Peripheral Neuropathy ◽  
Developmental Delay ◽  
De Novo ◽  
Refractory Epilepsy ◽  
De Novo Mutation ◽  
Global Developmental Delay ◽  
Missense Mutations ◽  
Related Protein ◽  
Resonance Imaging ◽  
Genetic Results

DNM1L encodes dynamin-related protein 1 (Drp1), which is a member of the dynamin superfamily of GTPases and mediates mitochondrial and peroxisomal fission. In humans, several de novo heterozygous missense mutations in DNM1L have been reported, which were characterized by devastating courses with refractory epilepsy, myoclonus, and brain atrophy on MRI. We describe a 4.5-year-old male child harboring a novel de novo mutation in DNM1L presenting a phenotype of developmental delay, ataxia, and peripheral neuropathy. The clinical features, magnetic resonance imaging findings, and genetic results were summarized. Meanwhile, all the cases of DNM1L mutations reported were reviewed. DNM1L variants may need to be considered in phenotypes that include global developmental delay, peripheral neuropathy, and ataxia.

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 A De Novo Mutation in DYRK1A Causes Syndromic Intellectual Disability: A Chinese Case Report

2019 ◽  
Vol 10 ◽  
Author(s):  
Fengchang Qiao ◽  
Binbin Shao ◽  
Chen Wang ◽  
Yan Wang ◽  
Ran Zhou ◽  
...  
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
De Novo ◽  
De Novo Mutation ◽  
Chinese Case

scholarly journals Are Mutations in the DHRS9 Gene Causally Linked to Epilepsy? A Case Report

Medicina ◽  
2020 ◽  
Vol 56 (8) ◽  
pp. 387
Author(s):  
Francesco Calì ◽  
Maurizio Elia ◽  
Mirella Vinci ◽  
Luigi Vetri ◽  
Edvige Correnti ◽  
...  
Keyword(s):  
Case Report ◽  
Protein Function ◽  
Early Onset ◽  
Neuronal Excitability ◽  
Compound Heterozygote ◽  
Aminobutyric Acid ◽  
Missense Mutations ◽  
Gamma Aminobutyric Acid ◽  
Whole Exome ◽  
Positive Modulator

The DHRS9 gene is involved in several pathways including the synthesis of allopregnanolone from progesterone. Allopregnanolone is a positive modulator of gamma aminobutyric acid (GABA) action and plays a role in the control of neuronal excitability and seizures. Whole-exome sequencing performed on a girl with an early onset epilepsy revealed that she was a compound heterozygote for two novel missense mutations of the DHRS9 gene likely to disrupt protein function. No previous studies have reported the implication of this gene in epilepsy. We discuss a new potential pathogenic mechanism underlying epilepsy in a child, due to a defective progesterone pathway.

scholarly journals A SMARCA2 Mutation in the First Case Report of Nicolaides-Baraitser Syndrome in Latin America: Genotype-Phenotype Correlation

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Ana Isabel Sánchez ◽  
Jorge Armando Rojas
Keyword(s):  
Latin America ◽  
Case Report ◽  
Language Impairment ◽  
De Novo ◽  
Signs And Symptoms ◽  
Facial Features ◽  
Missense Mutations ◽  
De Novo Mutations ◽  
Lower Lip ◽  
First Case

Nicolaides-Baraitser syndrome (NCBRS) is a rare and well-recognized entity that was first described in 1993, with a prevalence that is currently not known. It is recognized as a distinctive entity, with some variability in its signs and symptoms. The most important characteristics include intellectual disability, peculiar facial features including sparse scalp hair, coarse facial features, low frontal hairline, and microcephaly, and seizures. Additional features may include epicanthic folds, thin upper lip vermilion with thick lower lip vermilion, skeletal abnormalities, and severe language impairment. The disorder is inherited in an autosomal dominant manner caused by de novo mutations in the SMARCA2 gene, with most being missense mutations. We report a young adult patient with NCBRS and, to our knowledge, the first case report of the syndrome in Latin America with a confirmed molecular diagnosis and a mild-to-moderate phenotype.

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