Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuronal ceroid lipofuscinoses are a heterogeneous group of inherited degenerative disorders of the central nervous system. Cases of ceroid lipofuscinosis with cytoplasmic storage of granular osmiophilic deposits are associated with reduced activity of palmitoyl-protein thioesterase-1 (PPT-1) and mutations in CLN1, and occur from infancy to adulthood. We present clinical and diagnostic investigations in six children with variant late infantile neuronal ceroid lipofuscinosis and mutations in CLN1. The main clinical features at onset were behavioral disturbances and cognitive decline. Myoclonic jerks constituted the most prominent paroxysmal phenomenon. An electroencephalogram revealed the "vanishing" pattern described in infantile ceroid lipofuscinosis. Neurologic regression was associated with dramatic shrinkage of cortical structures, evident upon brain magnetic resonance imaging. Three unrelated children harboring the same homozygous mutation in CLN1 and a girl who carried a novel mutation resulting in skipping of multiple exons presented with a similar clinical phenotype. The most severe picture occurred in two siblings who carried a homozygous mutation predicting a prematurely truncated protein. Similar to the infantile form, the clinical evolution in this group of patients was characterized by an onset of severe neurologic impairment, peaking within a relatively short period of time, followed by a slower evolution of the disease.
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PMID:Variant late infantile neuronal ceroid lipofuscinosis because of CLN1 mutations. 1930 39

Infantile neuronal ceroid lipofuscinosis (INCL; NCL1, Haltia-Santavuori disease) is caused by mutations in the CLN1/PPT gene which are associated with an early onset INCL phenotype. The most detailed descriptions of INCL have come from Finland and a few series have been reported from southern European countries. Clinical course and follow-up of six Spanish patients with INCL are reported with the aim of assessing the chronological evolution and severity of this disease. The age at disease onset ranged from 8 to 15 months. Delayed motor skills were the initial symptom when the disease began before 12 months of age, and ataxia was the first sign when the disease began later. Cognitive decline, which is described between 12 and 18 months of age, occurred from 16 to 20 months of age. In our series early stage is characterized by motor impairment, cognitive decline and autistic features. Visual failure may appear simultaneously with the neurological symptoms, leading quickly to blindness. As reported, psychomotor regression appeared between 2 and 3 years of age. Myoclonic jerks occurred after 24 months of age and epilepsy was the last symptom of the disease. We report two novel mutations in a patient without epilepsy to date and describe the features of two siblings homozygous for the V181M (c.541G>A) mutation, associated with the most severe INCL phenotype. The clinical evolution might be helpful to identify patients affected by this rare disease. Early diagnosis is essential in order to provide genetic counselling to affected families. Our series may contribute to the study of the genotype-phenotype INCL correlation in the Mediterranean countries.
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PMID:Infantile neuronal ceroid lipofuscinosis: follow-up on a Spanish series. 2238 3

The neuronal ceroid-lipofuscinoses (NCL) is a group of neurodegenerative disorders characterized by epilepsy, visual failure, progressive mental and motor deterioration, myoclonus, dementia and reduced life expectancy. Classically, NCL-affected individuals have been classified into six categories, which have been mainly defined regarding the clinical onset of symptoms. However, some patients cannot be easily included in a specific group because of significant variation in the age of onset and disease progression. Molecular genetics has emerged in recent years as a useful tool for enhancing NCL subtype classification. Fourteen NCL genetic forms (CLN1 to CLN14) have been described to date. The variant late-infantile form of the disease has been linked to CLN5, CLN6, CLN7 (MFSD8) and CLN8 mutations. Despite advances in the diagnosis of neurodegenerative disorders mutations in these genes may cause similar phenotypes, which rends difficult accurate candidate gene selection for direct sequencing. Three siblings who were affected by variant late-infantile NCL are reported in the present study. We used whole-exome sequencing, direct sequencing and in silico approaches to identify the molecular basis of the disease. We identified the novel c.1219T>C (p.Trp407Arg) and c.1361T>C (p.Met454Thr) MFSD8 pathogenic mutations. Our results highlighted next generation sequencing as a novel and powerful methodological approach for the rapid determination of the molecular diagnosis of NCL. They also provide information regarding the phenotypic and molecular spectrum of CLN7 disease.
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PMID:Exome sequencing is an efficient tool for variant late-infantile neuronal ceroid lipofuscinosis molecular diagnosis. 2533 61

Neuronal ceroid lipofuscinoses (NCLs) are clinically and genetically heterogeneous neurodegenerative lysosomal diseases. Fourteen distinct NCL subtypes (CLN1-CLN14) are known, and they are caused by mutations in different genes. CLN8 was first identified in Finnish patients, and the phenotype was subsequently found in Turkish, Italian, and Pakistani patients. We report a 6-year-old Japanese boy with NCL with a novel missense mutation in CLN8. At the age of 3years, he manifested frequent drop seizures, and then progressively developed motor difficulties with an ataxic gait, myoclonus, left conjugate deviation, and rotational nystagmus. At age 5, he developed profound visual difficulty and dysphagia, and he has now lost his mobility. A bone marrow examination at age 5 showed sea-blue histiocytes. An electroretinogram was non-recordable. No giant somatosensory evoked potentials were found. Brain magnetic resonance imaging revealed bilateral diffuse hyperintensities in the white matter around the lateral ventricles and cerebellar and pontine atrophy on T2-weighted images. In a lysosomal enzyme study, the palmitoyl-protein-thioesterase and pepinase activity was within normal limits. Whole-exome sequencing revealed a homozygous CLN8 mutation: c.620T>G (p.L207R). His parents were both heterozygous for this mutation. To our knowledge, this is the first report of a CLN8 mutation in late infantile NCL in Japan.
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PMID:Novel missense mutation in CLN8 in late infantile neuronal ceroid lipofuscinosis: The first report of a CLN8 mutation in Japan. 2644 29