ABSTRACT
Over the past 68 years, the Finkel type late-onset adult autosomal dominant spinal muscular atrophy (SMA) that is allelic with amyotrophic lateral sclerosis-8 (ALS8) gained a ...genotype-phenotype correlation among the motor neuron diseases through the work of groups led by Zatz and Marques Jr.
Large expansions of microsatellite DNA cause several neurological diseases. In Spinocerebellar ataxia type 10 (SCA10), the repeat interruptions change disease phenotype; an (ATTCC)n or a ...(ATCCT)n/(ATCCC)n interruption within the (ATTCT)n repeat is associated with the robust phenotype of ataxia and epilepsy while mostly pure (ATTCT)n may have reduced penetrance. Large repeat expansions of SCA10, and many other microsatellite expansions, can exceed 10,000 base pairs (bp) in size. Conventional next generation sequencing (NGS) technologies are ineffective in determining internal sequence contents or size of these expanded repeats. Using repeat primed PCR (RP-PCR) in conjunction with a high-sensitivity pulsed-field capillary electrophoresis fragment analyzer (FEMTO-Pulse, Agilent, Santa Clara, CA) (RP-FEMTO hereafter), we successfully determined sequence content of large expansion repeats in genomic DNA of SCA10 patients and transformed yeast artificial chromosomes containing SCA10 repeats. This RP-FEMTO is a simple and economical methodology which could complement emerging NGS for very long sequence reads such as Single Molecule, Real-Time (SMRT) and nanopore sequencing technologies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cerebellar ataxia is a common finding in neurological practice and has a wide variety of causes, ranging from the chronic and slowly-progressive cerebellar degenerations to the acute cerebellar ...lesions due to infarction, edema and hemorrhage, configuring a true neurological emergency. Acute cerebellar ataxia is a syndrome that occurs in less than 72 hours, in previously healthy subjects. Acute ataxia usually results in hospitalization and extensive laboratory investigation. Clinicians are often faced with decisions on the extent and timing of the initial screening tests, particularly to detect treatable causes. The main group of diseases that may cause acute ataxias discussed in this article are: stroke, infectious, toxic, immune-mediated, paraneoplastic, vitamin deficiency, structural lesions and metabolic diseases. This review focuses on the etiologic and diagnostic considerations for acute ataxia.
Next-generation sequencing (NGS), comprising targeted panels (TP), exome sequencing (ES), and genome sequencing (GS) became robust clinical tools for diagnosing hereditary ataxia (HA). Determining ...their diagnostic yield (DY) is crucial for optimal clinical decision-making. We conducted a comprehensive systematic literature review on the DY of NGS tests for HA. We searched PubMed and Embase databases for relevant studies between 2016 and 2022 and manually examined reference lists of relevant reviews. Eligible studies described the DY of NGS tests in patients with ataxia as a significant feature. Data from 33 eligible studies showed a median DY of 43% (IQR = 9.5–100%). The median DY for TP and ES was 46% and 41.9%, respectively. Higher DY was associated with specific phenotype selection, such as episodic ataxia at 68.35% and early and late onset of ataxia at 46.4% and 54.4%. Parental consanguinity had a DY of 52.4% (
p
= 0.009), and the presumed autosomal recessive (AR) inheritance pattern showed 62.5%. There was a difference between the median DY of studies that performed targeted sequencing (tandem repeat expansion, TRE) screening and those that did not (
p
= 0.047). A weak inverse correlation was found between DY and the extent of previous genetic investigation (rho = − 0.323;
p
= 0.065). The most common genes were
CACNA1A
and
SACS
. DY was higher for presumed AR inheritance pattern, positive family history, and parental consanguinity. ES appears more advantageous due to the inclusion of rare genes that might be excluded in TP.
Keywords: autosomal-recessive cerebellar ataxias; ataxia; telangiectasia; movement disorders; alpha-fetoprotein Article Note: Relevant conflicts of interest/financial disclosures: The authors declare ...that there are no conflicts of interest relevant to this work. Funding agencies: No specific funding was received for this work. Byline: Helio A.G. Teive, Carlos H.F. Camargo, Renato P. Munhoz
When My Child Has Alzheimer's Disease Franklin, Gustavo L; Meira, Alex T; Barbosa, Maira Tonidandel ...
Journal of Alzheimer's disease,
01/2022, Letnik:
85, Številka:
1
Journal Article
Recenzirano
The significant increment in life expectancy, associated to the existence of high-performing older adults, and the appropriate diagnosis of early dementias, lead to an uncommon scenario, of healthy ...parents accompanying their children with Alzheimer's disease or another dementia to medical consultations. Here, we reported three peculiar clinical vignettes of patients diagnosed with a dementia, who were accompanied by healthy parents. This is a modern situation that tends to become more frequent, and must be properly discussed, since multidisciplinary care and specific training are necessary.
The authors present a historical review of spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), the most common form of spinocerebellar ataxia in Brazil, and consider the high frequency ...of cases in families from Itajaí, a city on the coast of the state of Santa Catarina with a large population of Portuguese/Azorean descent.
Autosomal recessive cerebellar ataxia type 1 (ARCA-1) or spinocerebellar ataxia autosomal recessive type 8 (SCAR8) is a slowly progressive neurodegenerative disorder that occurs due to mutations in ...the spectrin repeat containing nuclear envelope protein 1 (
SYNE1
) gene. Previously considered a rare cause of ARCA, related to French-Canadian patients from Beauce, Quebec, Canada,
SYNE1
ataxia is now known to be of worldwide distribution. We present the case report of a 54-year-old male patient with the genetic diagnosis of
SYNE1
ataxia, presenting with a
SYNE1
gene mutation never described in Chilean population before.
Neurodegeneration with brain iron accumulation (NBIA) represents a heterogeneous and complex group of inherited neurodegenerative diseases, characterized by excessive iron accumulation, particularly ...in the basal ganglia. Common clinical features of NBIA include movement disorders, particularly parkinsonism and dystonia, cognitive dysfunction, pyramidal signs, and retinal abnormalities. The forms of NBIA described to date include pantothenase kinase-associated neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN), neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein-associated neurodegeneration (MPAN), fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome. This review is a diagnostic approach for NBIA cases, from clinical features and brain imaging findings to the genetic etiology.
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