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.

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.

Homozygous Splice Mutation in CWF19L1 in Two Brothers with Autosomal Recessive Cerebellar Ataxia

2017 ◽  
Vol 48 (S 01) ◽  
pp. S1-S45
Author(s):  
A. Enderli ◽  
B. Heinrich ◽  
P. Joset ◽  
J. De Geyter ◽  
J. Scheer ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Autosomal Recessive ◽  
Splice Mutation ◽  
Autosomal Recessive Cerebellar Ataxia

The heterozygous deletion c.1509_1510delAG in exon 14 of FUS causes an aggressive childhood-onset ALS with cognitive impairment

2021 ◽  
Author(s):  
Paola Lanteri ◽  
Irene Meola ◽  
Antonio Canosa ◽  
Giovanni De Marco ◽  
Annarosa Lomartire ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Heterozygous Deletion ◽  
Childhood Onset

Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with a loss-of-function mutation in CDK5

2015 ◽  
Vol 134 (3) ◽  
pp. 305-314 ◽  
Author(s):  
Daniella Magen ◽  
Ayala Ofir ◽  
Liron Berger ◽  
Dorit Goldsher ◽  
Ayelet Eran ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cerebellar Hypoplasia ◽  
Loss Of Function

scholarly journals Ataxia with oculomotor apraxia type 2: an evolving axonal neuropathy

2017 ◽  
Vol 18 (1) ◽  
pp. 52-56
Author(s):  
Tahira N Choudry ◽  
David Hilton-Jones ◽  
Graham Lennox ◽  
Henry Houlden
Keyword(s):  
Autosomal Recessive ◽  
Age Of Onset ◽  
Axonal Neuropathy ◽  
Elevated Serum ◽  
Cerebellar Atrophy ◽  
Recessive Ataxia ◽  
Autosomal Recessive Ataxia ◽  
Oculomotor Apraxia ◽  
Ataxia With Oculomotor Apraxia

A 23-year-old woman had presented initially to a podiatrist complaining of poorly fitting shoes during her adolescence. After extensive neurological review, she was diagnosed with ataxia with oculomotor apraxia type 2. This is a progressive autosomal recessive ataxia associated with cerebellar atrophy, peripheral neuropathy and an elevated serum α-fetoprotein. Within Europe, it is the most frequent autosomal recessive ataxia after Friedreich’s ataxia and is due to mutations in the senataxin (SETX) gene. The age of onset is approximately 15 years.The diagnosis of oculomotor apraxia type 2 is often challenging. We provide a framework for assessing a young ataxic patient with or without oculomotor apraxia and review clues that will aid diagnosis. The prognosis, level of disability, cancer and immunosuppression risk all markedly differ between the conditions. Patients and their families need the correct diagnosis for genetic counselling, management and long-term surveillance with appropriate subspecialty services.

scholarly journals Biochemical Characterization of the GBA2 c.1780G>C Missense Mutation in Lymphoblastoid Cells from Patients with Spastic Ataxia

2018 ◽  
Vol 19 (10) ◽  
pp. 3099 ◽  
Author(s):  
Anna Malekkou ◽  
Maura Samarani ◽  
Anthi Drousiotou ◽  
Christina Votsi ◽  
Sandro Sonnino ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Autosomal Recessive ◽  
Biochemical Characterization ◽  
Fold Increase ◽  
Loss Of Function ◽  
Spastic Paraplegia ◽  
Spastic Ataxia ◽  
Autosomal Recessive Cerebellar Ataxia ◽  
Compensatory Effect

The GBA2 gene encodes the non-lysosomal glucosylceramidase (NLGase), an enzyme that catalyzes the conversion of glucosylceramide (GlcCer) to ceramide and glucose. Mutations in GBA2 have been associated with the development of neurological disorders such as autosomal recessive cerebellar ataxia, hereditary spastic paraplegia, and Marinesco-Sjogren-Like Syndrome. Our group has previously identified the GBA2 c.1780G>C [p.Asp594His] missense mutation, in a Cypriot consanguineous family with spastic ataxia. In this study, we carried out a biochemical characterization of lymphoblastoid cell lines (LCLs) derived from three patients of this family. We found that the mutation strongly reduce NLGase activity both intracellularly and at the plasma membrane level. Additionally, we observed a two-fold increase of GlcCer content in LCLs derived from patients compared to controls, with the C16 lipid being the most abundant GlcCer species. Moreover, we showed that there is an apparent compensatory effect between NLGase and the lysosomal glucosylceramidase (GCase), since we found that the activity of GCase was three-fold higher in LCLs derived from patients compared to controls. We conclude that the c.1780G>C mutation results in NLGase loss of function with abolishment of the enzymatic activity and accumulation of GlcCer accompanied by a compensatory increase in GCase.

Impact of age of onset of illness on clinical phenotype in OCD

2012 ◽  
Vol 200 (2-3) ◽  
pp. 554-559 ◽  
Author(s):  
Janardhanan C. Narayanaswamy ◽  
Biju Viswanath ◽  
Anish Veshnal Cherian ◽  
Suresh Bada Math ◽  
Thennarasu Kandavel ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Clinical Phenotype

scholarly journals A case of atypical systemic primary carnitine deficiency in Saudi Arabia

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Abdulrahman Alghamdi ◽  
Hani Almalki ◽  
Aiman Shawli ◽  
Rahaf Waggass ◽  
Fahad Hakami
Keyword(s):  
Dilated Cardiomyopathy ◽  
Autosomal Recessive ◽  
Acid Metabolism ◽  
Age Of Onset ◽  
Carnitine Deficiency ◽  
Proximal Muscle ◽  
Skeletal Myopathy ◽  
Primary Carnitine Deficiency ◽  
Elevated Transaminases ◽  
Work Up

Systemic primary carnitine deficiency (SPCD) is an autosomal recessive inborn error of fatty acid metabolism caused by a defect in the transporter responsible for moving carnitine across plasma membrane. The clinical features of SPCD vary widely based on the age of onset and organs involved. During infancy, patients might show episodes of hypoketotic hypoglycemia, hepatomegaly, elevated transaminases, and hyperammonemia. Skeletal myopathy, elevated creatine kinase, and cardiomyopathy are the main manifestations in children with SPCD, while in adults, the disorder is usually manifested as cardiomyopathy, arrhythmias, or fatigability. Here, we report a 5-year-old boy with SPCD that presented as dilated cardiomyopathy with atypical features, such as anemia, respiratory distress, and proximal muscle weakness. This report supports considering carnitine deficiency treatment in the work-up of unexplained pediatric dilated cardiomyopathy.

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.

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