scholarly journals The first missense alteration in the MCPH1 gene causes autosomal recessive microcephaly with an extremely mild cellular and clinical phenotype

2005 ◽  
Vol 26 (5) ◽  
pp. 496-496 ◽  
Author(s):  
Marc Trimborn ◽  
Reyk Richter ◽  
Nadine Sternberg ◽  
Ioannis Gavvovidis ◽  
Detlev Schindler ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Clinical Phenotype ◽  
Missense Alteration

scholarly journals Monogenic Causes of Strokes

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1855
Author(s):  
Justyna Chojdak-Łukasiewicz ◽  
Edyta Dziadkowiak ◽  
Sławomir Budrewicz
Keyword(s):  
Autosomal Recessive ◽  
Genetic Factors ◽  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Clinical Phenotype ◽  
Single Gene ◽  
Monogenic Disorders ◽  
Single Gene Disorders ◽  
Appropriate Therapy

Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available.

scholarly journals GPT2 mutations in autosomal recessive developmental disability: extending the clinical phenotype and population prevalence estimates

2019 ◽  
Vol 138 (10) ◽  
pp. 1183-1200
Author(s):  
Qing Ouyang ◽  
Brian C. Kavanaugh ◽  
Lena Joesch-Cohen ◽  
Bethany Dubois ◽  
Qing Wu ◽  
...  
Keyword(s):  
Developmental Disability ◽  
Autosomal Recessive ◽  
Clinical Phenotype ◽  
Population Prevalence ◽  
Prevalence Estimates

scholarly journals SYNE1-related autosomal recessive cerebellar ataxia, congenital cerebellar hypoplasia, and cognitive impairment

2018 ◽  
Author(s):  
Lauren Swan ◽  
John Cardinal ◽  
David Coman
Keyword(s):  
Cognitive Impairment ◽  
Autosomal Recessive ◽  
Age Of Onset ◽  
Clinical Phenotype ◽  
Cerebellar Hypoplasia ◽  
Childhood Onset ◽  
Spectrin Repeat ◽  
Disease Phenotypes ◽  
Related Disease ◽  
Autosomal Recessive Cerebellar Ataxia

The spectrin repeat-containing nuclear envelope protein 1 (SYNE1) gene encodes a family of spectrin structural proteins that are associated with anchoring the plasma membrane to the actin cytoskeleton. SYNE1-related disease is most commonly reported in autosomal recessive spinocerebellar ataxia 8, which demonstrates variable age of onset with a median of 30 years of age. However pathogenic mutations in SYNE1 are also causative of arthrogryposis multiplex congenital, a severe congenital neuromuscular condition. Here in we report monozygous twins with childhood onset ataxia, cerebellar hypoplasia, dysarthria, and cognitive impairment sharing two novel heterozygous mutations in the SYNE1 gene. Our family may expand the clinical phenotype associated with SYNE1-related disease and offers possible genotype-phenotype correlations of a rare continuum of clinical disease phenotypes from neonatal to adult onset.

scholarly journals Expanding the clinical phenotype associated with NIPAL4 mutation: Study of a Tunisian consanguineous family with erythrokeratodermia variabilis—Like Autosomal Recessive Congenital Ichthyosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258777
Author(s):  
Cherine Charfeddine ◽  
Nadia Laroussi ◽  
Rahma Mkaouar ◽  
Raja Jouini ◽  
Olfa Khayat ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Mutational Analysis ◽  
Clinical Phenotype ◽  
Homozygous Mutation ◽  
Congenital Ichthyosis ◽  
Whole Exome ◽  
Genes Encoding ◽  
Autosomal Recessive Congenital Ichthyosis ◽  
Connexin Genes ◽  
Disorder Of Cornification

Erythrokeratodermia variabilis (EKV) is a rare disorder of cornification usually associated with dominant mutations in the GJB3 and GJB4 genes encoding connexins (Cx)31 and 30.3. Genetic heterogeneity of EKV has already been suggested. We investigated at the clinical and genetic level a consanguineous Tunisian family with 2 sisters presenting an autosomal recessive form of EKV to better characterize this disease. Mutational analysis initially screened the connexin genes and Whole-exome sequencing (WES) was performed to identify the molecular aetiology of the particular EKV phenotype in the proband. Migratory shaped erythematous areas are the initial presenting sign followed by relatively stable hyperkeratotic plaques are the two predominates characteristics in both patients. However, remarkable variability of morphological and dominating features of the disease were observed between patients. In particular, the younger sister (proband) exhibited ichthyosiform-like appearance suggesting Autosomal Recessive Congenital Ichthyosis (ARCI) condition. No causative mutations were detected in the GJB3 and GJB4 genes. WES results revealed a novel missense homozygous mutation in NIPAL4 gene (c.835C>G, p.Pro279Ala) in both patients. This variant is predicted to be likely pathogenic. In addition, in silico analysis of the mutated 3D domain structure predicted that this variant would result in NIPA4 protein destabilization and Mg2+ transport perturbation, pointing out the potential role of NIPAL4 gene in the development and maintenance of the barrier function of the epidermis. Taken togheter, these results expand the clinical phenotype associated with NIPAL4 mutation and reinforce our hypothesis of NIPAL4 as the main candidate gene for the EKV-like ARCI phenotype.

scholarly journals Cell-based analysis of CAD variants identifies individuals likely to benefit from uridine therapy

2020 ◽  
Vol 22 (10) ◽  
pp. 1598-1605 ◽  
Author(s):  
Francisco del Caño-Ochoa ◽  
Bobby G. Ng ◽  
Malak Abedalthagafi ◽  
Mohammed Almannai ◽  
Ronald D. Cohn ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Clinical Presentation ◽  
De Novo ◽  
Clinical Phenotype ◽  
Transient Transfection ◽  
Missense Variants ◽  
De Novo Biosynthesis ◽  
Pathogenic Variants ◽  
Large Size ◽  
A Cell

Abstract Purpose Pathogenic autosomal recessive variants in CAD, encoding the multienzymatic protein initiating pyrimidine de novo biosynthesis, cause a severe inborn metabolic disorder treatable with a dietary supplement of uridine. This condition is difficult to diagnose given the large size of CAD with over 1000 missense variants and the nonspecific clinical presentation. We aimed to develop a reliable and discerning assay to assess the pathogenicity of CAD variants and to select affected individuals that might benefit from uridine therapy. Methods Using CRISPR/Cas9, we generated a human CAD-knockout cell line that requires uridine supplements for survival. Transient transfection of the knockout cells with recombinant CAD restores growth in absence of uridine. This system determines missense variants that inactivate CAD and do not rescue the growth phenotype. Results We identified 25 individuals with biallelic variants in CAD and a phenotype consistent with a CAD deficit. We used the CAD-knockout complementation assay to test a total of 34 variants, identifying 16 as deleterious for CAD activity. Combination of these pathogenic variants confirmed 11 subjects with a CAD deficit, for whom we describe the clinical phenotype. Conclusions We designed a cell-based assay to test the pathogenicity of CAD variants, identifying 11 CAD-deficient individuals who could benefit from uridine therapy.

scholarly journals Novel PANK2 mutation in the first Greek compound heterozygote patient with pantothenate-kinase-associated neurodegeneration

2017 ◽  
Vol 5 ◽  
pp. 2050313X1772010
Author(s):  
George P Paraskevas ◽  
Christos Yapijakis ◽  
Anastasia Bougea ◽  
Vasilios Constantinides ◽  
Mara Bourbouli ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Rare Variants ◽  
Disease Risk ◽  
Clinical Phenotype ◽  
Compound Heterozygote ◽  
Brain Iron ◽  
Pantothenate Kinase ◽  
Autosomal Recessive Form ◽  
Recessive Form

Pantothenate-kinase-associated neurodegeneration is the most common autosomal recessive form of neurodegeneration with brain iron accumulation. Less than 100 mutations in PANK2 gene (20p13) are responsible for classic and atypical cases. We report here the first Greek case of atypical pantothenate-kinase-associated neurodegeneration, confirmed by molecular analysis that revealed two trans-acting mutations. Our findings highlight the possible role of rare variants contributing to disease risk and possibly to variable clinical phenotype.

scholarly journals TRAPPC9-related autosomal recessive intellectual disability: report of a new mutation and clinical phenotype

2012 ◽  
Vol 21 (2) ◽  
pp. 229-232 ◽  
Author(s):  
Giuseppe Marangi ◽  
Vincenzo Leuzzi ◽  
Filippo Manti ◽  
Serena Lattante ◽  
Daniela Orteschi ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Autosomal Recessive ◽  
Clinical Phenotype ◽  
New Mutation

scholarly journals Fanconi Anemia Proteins FANCA, FANCC, and FANCG/XRCC9 Interact in a Functional Nuclear Complex

1999 ◽  
Vol 19 (7) ◽  
pp. 4866-4873 ◽  
Author(s):  
Irene Garcia-Higuera ◽  
Yanan Kuang ◽  
Dieter Näf ◽  
Jennifer Wasik ◽  
Alan D. D’Andrea
Keyword(s):  
Nuclear Localization ◽  
Fanconi Anemia ◽  
Autosomal Recessive ◽  
Nuclear Protein ◽  
Cancer Susceptibility ◽  
Clinical Phenotype ◽  
Normal Cells ◽  
Amino Terminal ◽  
Nuclear Complex ◽  
Complementation Groups

ABSTRACT Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least eight complementation groups (A to H). Three FA genes, corresponding to complementation groups A, C, and G, have been cloned, but their cellular function remains unknown. We have previously demonstrated that the FANCA and FANCC proteins interact and form a nuclear complex in normal cells, suggesting that the proteins cooperate in a nuclear function. In this report, we demonstrate that the recently cloned FANCG/XRCC9 protein is required for binding of the FANCA and FANCC proteins. Moreover, the FANCG protein is a component of a nuclear protein complex containing FANCA and FANCC. The amino-terminal region of the FANCA protein is required for FANCG binding, FANCC binding, nuclear localization, and functional activity of the complex. Our results demonstrate that the three cloned FA proteins cooperate in a large multisubunit complex. Disruption of this complex results in the specific cellular and clinical phenotype common to most FA complementation groups.

Double trouble: a case of an ataxic young man with coeliac disease and cerebrotendinous xanthomatosis

2020 ◽  
Vol 13 (12) ◽  
pp. e237978
Author(s):  
Jordan Burgess ◽  
Diba Behzad-Noori ◽  
Cheryl Longman ◽  
Kathryn Brennan
Keyword(s):  
Cognitive Impairment ◽  
Coeliac Disease ◽  
South Asian ◽  
Autosomal Recessive ◽  
Clinical Phenotype ◽  
Consanguineous Marriage ◽  
Cerebrotendinous Xanthomatosis ◽  
Close Attention ◽  
Delay In Diagnosis ◽  
Autosomal Recessive Condition

We present the case of a 29-year-old south Asian man born of consanguineous marriage, presenting with ataxia, peripheral neuropathy and cognitive impairment. An initial diagnosis of coeliac disease was thought to explain the pertinent clinical features; however, further investigation led to an additional diagnosis of the rare yet treatable autosomal recessive condition, cerebrotendinous xanthomatosis. With both conditions employing highly diverse and overlapping clinical phenotypes, this contributed to a delay in diagnosis. Our report highlights the importance of paying close attention to both the clinical phenotype and family history.

Agammaglobulinemia: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management

2020 ◽  
Vol 20 (9) ◽  
pp. 1434-1447
Author(s):  
Salar Pashangzadeh ◽  
Reza Yazdani ◽  
Farzad Nazari ◽  
Gholamreza Azizi ◽  
Hassan Abolhassani ◽  
...  
Keyword(s):  
Serum Level ◽  
Peripheral Blood ◽  
Autosomal Recessive ◽  
Respiratory Infections ◽  
Clinical Phenotype ◽  
Clinical Manifestations ◽  
Therapeutic Strategies ◽  
Gastrointestinal Complications ◽  
Primary Antibody Deficiencies ◽  
Severe Reduction

Agammaglobulinemia is a type of primary antibody deficiencies, characterized by severe reduction in serum level of all types of immunoglobulins level and absence of B cells in the peripheral blood. X-linked and various autosomal recessive/dominant mutations have been identified underlying the pathogenesis of this disorder. Affected patients present a broad range of clinical manifestations, including respiratory infections, gastrointestinal complications, Enterovirus infections, autoimmunity, and malignancies. This disease can be controlled by different therapeutic strategies. In this review, we describe different aspects of agammaglobulinemia such as epidemiology, pathogenesis, clinical phenotype, diagnosis, management, and prognosis of congenital agammaglobulinemia.

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