scholarly journals Ataxias with Autosomal, X-Chromosomal or Maternal Inheritance

2009 ◽  
Vol 36 (4) ◽  
pp. 409-428 ◽  
Author(s):  
Josef Finsterer
Keyword(s):  
Ataxia Telangiectasia ◽  
Large Scale ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Late Onset ◽  
Fragile X ◽  
Axonal Neuropathy ◽  
Friedreich Ataxia ◽  
Point Mutations ◽  
Spinocerebellar Ataxias

Heredoataxias are a group of genetic disorders with a cerebellar syndrome as the leading clinical manifestation. The current classification distinguishes heredoataxias according to the trait of inheritance into autosomal dominant, autosomal recessive, X-linked, and maternally inherited heredoataxias. The autosomal dominant heredoataxias are separated into spinocerebellar ataxias (SCA1-8, 10-15, 17-23, 25-30, and dentato-rubro-pallido-luysian atrophy), episodic ataxias (EA1-7), and autosomal dominant mitochondrial heredoataxias (Leigh syndrome, MIRAS, ADOAD, and AD-CPEO). The autosomal recessive ataxias are separated into Friedreich ataxia, ataxia due to vitamin E deficiency, ataxia due to Abeta-lipoproteinemia, Refsum disease, late-onset Tay-Sachs disease, cerebrotendineous xanthomatosis, spinocerebellar ataxia with axonal neuropathy, ataxia telangiectasia, ataxia telangiectasia-like disorder, ataxia with oculomotor apraxia 1 and 2, spastic ataxia of Charlevoix-Saguenay, Cayman ataxia, Marinesco-Sjögren syndrome, and autosomal recessive mitochondrial ataxias (AR-CPEO, SANDO, SCAE, AHS, IOSCA, MEMSA, LBSL CoQ-deficiency, PDC-deficiency). Only two of the heredoataxias, fragile X/tremor/ataxia syndrome, and XLSA/A are transmitted via an X-linked trait. Maternally inherited heredoataxias are due to point mutations in genes encoding for tRNAs, rRNAs, respiratory chain subunits or single large scale deletions/duplications of the mitochondrial DNA and include MELAS, MERRF, KSS, PS, MILS, NARP, and non-syndromic mitochondrial disorders. Treatment of heredoataxias is symptomatic and supportive and may have a beneficial effect in single patients.**Please see page 424 for abbreviation list.

Inherited Ataxias

2015 ◽  
Author(s):  
Susan Perlman
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Friedreich Ataxia ◽  
Spinocerebellar Ataxias ◽  
Recessive Ataxia ◽  
Internet Resources ◽  
Genetic Abnormalities ◽  
Repeat Expansions ◽  
The Common ◽  
Inherited Ataxias

The inherited ataxias are disorders that cause progressive imbalance as a result of pathology in the cerebellum and its various connecting pathways. Autosomal recessive ataxias include Friedreich ataxia, ataxia with isolated vitamin E deficiency, ataxia-telangiectasia, and autosomal recessive ataxia of Charlevoix-Saguenay, among others. A discussion of autosomal dominant ataxias covers spinocerebellar ataxias (SCA) types 1 through 14, dentatorubral pallidoluysian atrophy (DRPLA), and episodic ataxia (EA) syndromes. Clinical features, laboratory studies, differential diagnosis, and management of inherited ataxias are discussed. Tables describe both autosomal recessive ataxias and autosomal dominant ataxias (with known gene loci), childhood– or young adult–onset ataxias with ill-defined genetic abnormalities, phenotypic features that may indicate a specific genotype in the common autosomal dominant ataxias, and normal and expanded ranges of various repetitive nucleotide sequences in inherited ataxias. Figures include a diagrammatic representation of the type of repeat expansions associated with ataxias, aggregates of ataxin 3, a schematic of some of the proposed pathogenic mechanisms in the polyglutamine ataxias, and dystonia in a patient with SCA3. A sidebar offers selected Internet resources for information on ataxias. This chapter contains 64 references.

scholarly journals Adult Onset Spinocerebellar Ataxia in a Canadian Movement Disorders Clinic

2005 ◽  
Vol 32 (4) ◽  
pp. 450-458 ◽  
Author(s):  
Scott Kraft ◽  
Sarah Furtado ◽  
Ranjit Ranawaya ◽  
Jillian Parboosingh ◽  
Stacey Bleoo ◽  
...  
Keyword(s):  
Family History ◽  
Movement Disorders ◽  
Autosomal Recessive ◽  
Fragile X ◽  
Positive Family History ◽  
Friedreich Ataxia ◽  
Genetic Diagnosis ◽  
Common Mutation ◽  
Adult Onset ◽  
Spinocerebellar Ataxias

ABSTRACT:Background:The spinocerebellar ataxias (SCAs) are a genetically and clinically heterogeneous group of neurodegenerative disorders. Relative frequencies vary within different ethnic groups and geographical locations.Objectives:1) To determine the frequencies of hereditary and sporadic adult onset SCAs in the Movement Disorders population; 2) to assess if the fragile X mental retardation gene 1 (FMR1) premutation is found in this population.Methods:A retrospective chart review of individuals with a diagnosis of adult onset SCA was carried out. Testing for SCA types 1, 2, 3, 6, 7, and 8, Dentatorubral-pallidoluysian atrophy (DRPLA), Friedreich ataxia and the FMR1 expansion was performed.Results:A total of 69 patients in 60 families were identified. Twenty-one (35%) of the families displayed autosomal dominant and two (3.3%) showed autosomal recessive (AR) pattern of inheritance. A positive but undefined family history was noted in nine (15%). The disorder appeared sporadic in 26 patients (43.3%). In the AD families, the most common mutation was SCA3 (23.8%) followed by SCA2 (14.3%) and SCA6 (14.3%). The SCA1 and SCA8 were each identified in 4.8%. FA was found in a pseudodominant pedigree, and one autosomal recessive pedigree. One sporadic patient had a positive test (SCA3).Dentatorubral-pallidoluysian atrophy and FMR1 testing was negative.Conclusion:A positive family history was present in 53.3% of our adult onset SCA patients. A specific genetic diagnosis could be given in 61.9% of dominant pedigrees with SCA3 being the most common mutation, followed by SCA2 and SCA6. The yield in sporadic cases was low. The fragile X premutation was not found to be responsible for SCA.

Characterising the phenotype and mode of inheritance of patients with inherited peripheral neuropathies carrying MME mutations

2018 ◽  
Vol 55 (12) ◽  
pp. 814-823 ◽  
Author(s):  
Vincenzo Lupo ◽  
Marina Frasquet ◽  
Ana Sánchez-Monteagudo ◽  
Ana Lara Pelayo-Negro ◽  
Tania García-Sobrino ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Late Onset ◽  
Axonal Neuropathy ◽  
Genetic Diagnosis ◽  
Hereditary Neuropathy ◽  
Motor Neuropathy ◽  
Charcot Marie Tooth Disease ◽  
Hereditary Motor Neuropathy ◽  
Index Cases ◽  
Mode Of Inheritance

BackgroundMutations in the metalloendopeptidase (MME) gene were initially identified as a cause of autosomal recessive Charcot-Marie-Tooth disease type 2 (CMT2). Subsequently, variants in MME were linked to other late-onset autosomal dominant polyneuropathies. Thus, our goal was to define the phenotype and mode of inheritance of patients carrying changes in MME.MethodsWe screened 197 index cases with a hereditary neuropathy of the CMT type or distal hereditary motor neuropathy (dHMN) and 10 probands with familial amyotrophic lateral sclerosis (fALS) using a custom panel of 119 genes. In addition to the index case subjects, we also studied other clinically and/or genetically affected and unaffected family members.ResultsWe found 17 variants in MME in a total of 20 index cases, with biallelic MME mutations detected in 13 cases from nine families (three in homozygosis and six in compound heterozygosis) and heterozygous variants found in 11 families. All patients with biallelic variants had a similar phenotype, consistent with late-onset axonal neuropathy. Conversely, the phenotype of patients carrying heterozygous mutations was highly variable [CMT type 1 (CMT1), CMT2, dHMN and fALS] and mutations did not segregate with the disease.ConclusionMME mutations that segregate in an autosomal recessive pattern are associated with a late-onset CMT2 phenotype, yet we could not demonstrate that MME variants in heterozygosis cause neuropathy. Our data highlight the importance of establishing an accurate genetic diagnosis in patients carrying MME mutations, especially with a view to genetic counselling.

scholarly journals Clinical Characteristics and In Vitro Analysis of MYO6 Variants Causing Late-onset Progressive Hearing Loss

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 273
Author(s):  
Shin-ichiro Oka ◽  
Timothy F. Day ◽  
Shin-ya Nishio ◽  
Hideaki Moteki ◽  
Maiko Miyagawa ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Clinical Characteristics ◽  
Large Scale ◽  
Autosomal Dominant ◽  
Late Onset ◽  
Site Directed Mutagenesis ◽  
Molecular Characteristics ◽  
Progressive Hearing Loss ◽  
Cochlear Hair Cells

MYO6 is known as a genetic cause of autosomal dominant and autosomal recessive inherited hearing loss. In this study, to clarify the frequency and clinical characteristics of hearing loss caused by MYO6 gene mutations, a large-scale genetic analysis of Japanese patients with hearing loss was performed. By means of massively parallel DNA sequencing (MPS) using next-generation sequencing for 8074 Japanese families, we found 27 MYO6 variants in 33 families, 22 of which are novel. In total, 2.40% of autosomal dominant sensorineural hearing loss (ADSNHL) in families in this study (32 out of 1336) was found to be caused by MYO6 mutations. The present study clarified that most cases showed juvenile-onset progressive hearing loss and their hearing deteriorated markedly after 40 years of age. The estimated hearing deterioration was found to be 0.57 dB per year; when restricted to change after 40 years of age, the deterioration speed was accelerated to 1.07 dB per year. To obtain supportive evidence for pathogenicity, variants identified in the patients were introduced to MYO6 cDNA by site-directed mutagenesis and overexpressed in epithelial cells. They were then assessed for their effects on espin1-induced microvilli formation. Cells with wildtype myosin 6 and espin1 co-expressed created long microvilli, while co-expression with mutant constructs resulted in severely shortened microvilli. In conclusion, the present data clearly showed that MYO6 is one of the genes to keep in mind with regard to ADSNHL, and the molecular characteristics of the identified gene variants suggest that a possible pathology seems to result from malformed stereocilia of the cochlear hair cells.

Cerebellar Disorders and Ataxias: Inherited Disorders

2021 ◽  
pp. 618-631
Author(s):  
Anhar Hassan
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Fragile X ◽  
Cerebellar Atrophy ◽  
Clinical Approach ◽  
Inherited Disorders ◽  
Inherited Ataxias ◽  
Ataxia Syndrome ◽  
Cerebellar Disorders

Disorders of the cerebellum or its circuitry can result in ataxia. These disorders may be acquired or inherited. Inherited ataxias may be autosomal recessive (eg. Friedrich ataxia), autosomal dominant (eg, spinal cerebellar atrophy) or X linked (eg, fragile X–associated ataxia syndrome). Chapter 73 (“Cerebellar Disorders and Ataxias: Acquired Disorders”) reviews the clinical approach to patients with ataxia and discusses acquired forms of ataxia. This chapter reviews clinical approaches, diagnostic details, and treatment of inherited ataxias.

scholarly journals Clinical and molecular characteristics of a Brazilian family with spinocerebellar ataxia type 1

1996 ◽  
Vol 54 (3) ◽  
pp. 412-418 ◽  
Author(s):  
Iscia Lopes-Cendes ◽  
Carlos E. Steiner ◽  
Isabel Silveira ◽  
Walter Pinto-Junior ◽  
Jayme A. Maciel ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Late Onset ◽  
Cag Repeat ◽  
Spinocerebellar Ataxia Type ◽  
Molecular Characteristics ◽  
Spinocerebellar Ataxias ◽  
Dominant Type ◽  
Expanded Allele ◽  
Mean Size ◽  
Autosomal Dominant Type

The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of late onset neurodegenerative disorders. To date, seven different genes causing autosomal dominant SCA have been mapped: SCA1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5, SCA7 and dentatorubropallidoluysian atrophy (DRPLA). Expansions of an unstable trinucleotide CAG repeat cause three of these disorders: SCA1, MJD/SCA3 and DRPLA. We studied one Brazilian family segregating an autosomal dominant type of SCA. A total of ten individuals were examined and tested for the presence of the SCA1, MJD and DRPLA mutations. Three individuals, one male and two females, were considered affected based on neurological examination; ages at onset were: 32, 36 and 41 years. The first complaint in all three patients was gait ataxia which progressed slowly over the years. Six individuals showed one allele containing an expanded CAG repeat in the SCA1 gene. The mean size of the expanded allele was 48.2 CAG units. Instability of the expanded CAG tract was seen in the two transmissions that were observed in this family. In both occasions there was a contraction of the CAG tract. Our study demonstrates that SCA1 occurs in the Brazilian population. In addition, our results stress the importance of molecular studies in the confirmation of diagnosis and for pre-symptomatic testing in SCAs.

Can progression of autosomal dominant or autosomal recessive polycystic kidney disease be prevented?

2001 ◽  
Vol 21 (5) ◽  
pp. 430-440 ◽  
Author(s):  
Ira D. Davis ◽  
Katherine MacRae Dell ◽  
William E. Sweeney ◽  
Ellis D. Avner
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Polycystic Kidney

Late onset autosomal dominant hypophosphatemic rickets; confirmation of the diagnosis with genomic analysis

2013 ◽  
Author(s):  
Symeon Tournis ◽  
Ioannis Stathopoulos ◽  
Kalliopi Lampropoulou-Adamidou ◽  
Theodora Koromila ◽  
Nikolaos Chatzistamatas ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Late Onset ◽  
Genomic Analysis ◽  
Hypophosphatemic Rickets ◽  
Autosomal Dominant Hypophosphatemic Rickets

CANVAS is a common form of late-onset hereditary ataxia

2020 ◽  
pp. 51-52
Author(s):  
Е.П. Нужный ◽  
Н.Ю. Абрамычева ◽  
Е.Г. Воробьева ◽  
Е.О. Иванова ◽  
Ю.А. Шпилюкова ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Clinical Picture ◽  
Autosomal Recessive ◽  
Late Onset ◽  
Repeat Expansion ◽  
Hereditary Ataxia ◽  
Recessive Ataxia ◽  
Autosomal Recessive Ataxia

Синдром CANVAS (мозжечковая атаксия, невропатия и вестибулярная арефлексия) - аутосомно-рецессивная атаксия с поздним дебютом, обусловленная носительством биаллельной экспансии (AAGGG)n во 2-м интроне гена RFC1. До настоящего момента отсутствуют сведения о распространенности данного заболевания в российских семьях. Нами был проведен поиск биаллельной экспансии AAGGG-повторов у 35 российских пациентов с поздней мозжечковой атаксией. Верифицированы 5 пациентов (14,3%) с синдромом CANVAS и характерной клинической картиной. CANVAS (cerebellar ataxia, neuropathy and vestibular areflexia) is a late-onset autosomal recessive ataxia due to biallelic (AAGGG)n repeat expansion in the 2nd intron of the RFC1 gene. There is no information on the CANVAS prevalence in Russian families. We searched for biallelic expansion of AAGGG repeats in 35 Russian patients with late-onset cerebellar ataxia. Five patients (14.3%) with CANVAS syndrome and a characteristic clinical picture were verified.

Sign in / Sign up

Export Citation Format

Share Document