Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurodegeneration with brain iron accumulation (NBIA) is etiologically, clinically, and by imaging a heterogeneous group including NBIA types 1 [pantothenate kinase-associated neurodegeneration (PKAN)] and 2 (PLA2G6-associated neurodegeneration), neuroferritinopathy, and aceruloplasminaemia. Data on genetically defined Indian-subcontinent NBIA cases are limited. We report 6 patients from the Indian-subcontinent with a movement disorder and MRI basal ganglia iron deposition, compatible with diagnosis of an NBIA syndrome. All patients were screened for abnormalities in serum ceruloplasmin and ferritin levels and mutations in NBIA-associated genes [pantothenate kinase 2 (PANK2), PLA2G6 and ferritin light chain (exon 4)]. We present clinical, imaging and genetic data correlating phenotype-genotype relations. Four patients carried PANK2 mutations, two of these were novel. The clinical phenotype was mainly dystonic with generalized dystonia and marked orobulbar features in the 4 adolescent-onset cases. One of the four had a late-onset (age 37) unilateral jerky postural tremor. His mutation, c.1379C>T, appears associated with a milder phenotype. Interestingly, he developed the eye-of-the-tiger sign only 10 years after onset. Two of the six presented with adult-onset levodopa (L-dopa)-responsive asymmetric re-emergent rest tremor, developing L-dopa-induced dyskinesias, and good benefit to deep brain stimulation (in one), thus resembling Parkinson's disease (PD). Both had an eye-of-the-tiger sign on MRI but were negative for known NBIA-associated genes, suggesting the existence of further genetic or sporadic forms of NBIA syndromes. In conclusion, genetically determined NBIA cases from the Indian subcontinent suggest presence of unusual phenotypes of PANK2 and novel mutations. The phenotype of NBIA of unknown cause includes a PD-like presentation.
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PMID:Indian-subcontinent NBIA: unusual phenotypes, novel PANK2 mutations, and undetermined genetic forms. 2062 44

Around 15% of patients with Parkinson's disease (PD) have a family history, and 5-10% have confirmed genetic causes. PRKN is the most common gene responsible for early-onset Parkinson's disease (EOPD), while rare variants of PLA2G6 likely raise PD susceptibility in the Chinese population. We investigated the genetic information of 13 members of a Han Chinese family with known EOPD by whole-exome sequencing and Sanger sequencing, and analyzed the clinical history, physical examination, blood laboratory test, and brain imaging data of the patients. Two members, including the proband, were suspected of having EOPD. A novel homozygous frameshift mutation, c.856delT, and a compound heterozygous mutation, c.1321T>C/c.856delT of PRKN, were identified, as well as two single nucleotide variants of PLA2G6 and TENM4. The proband exhibited a rare symmetrical resting tremor limited to her lower limbs and never exhibited signs of rigidity. 18F-DOPA PET/CT scan indicated a symmetrical reduced signaling in the striatum. The novel frameshift mutation and compound heterozygous mutation of PRKN are likely to be the genetic causes of EOPD in this family.
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PMID:A Han Chinese Family With Early-Onset Parkinson's Disease Carrying Novel Frameshift Mutation and Compound Heterozygous Mutation of PRKN Appearing Incompatible With MDS Clinical Diagnostic Criteria. 3315 36