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Unusual Phenotype (unusual + phenotype)

Distribution by Scientific Domains

Medical Sciences	83%

Selected Abstracts

Indian-subcontinent NBIA: Unusual phenotypes, novel PANK2 mutations, and undetermined genetic forms ,

MOVEMENT DISORDERS, Issue 10 2010
Annu Aggarwal MD
Abstract 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. © 2010 Movement Disorder Society [source]

An Xp; Yq Translocation Causing a Novel Contiguous Gene Syndrome in Brothers with Generalized Epilepsy, Ichthyosis, and Attention Deficits

EPILEPSIA, Issue 12 2003
Michael J. Doherty
Summary:,Purpose: We describe two brothers with generalized epilepsy, attention deficits, congenital ichthyosis, and Leri,Weill dyschondrosteosis who harbor an unusual Xp; Yq translocation chromosome, resulting in a novel contiguous gene syndrome because of deletion of genes from the distal short arm of the X chromosome. Methods: Physical examination, neuropsychologic testing, EEG, and neuroimaging studies were performed. Because of their unusual phenotype, karyotyping, fluorescence in situ hybridization, and further molecular analyses were carried out to refine the break points of the underlying unbalanced sex chromosome rearrangement. Results: The subjects had generalized epilepsy, X-linked ichthyosis, Madelung deformities, mesomelia, normal intelligence, and attention deficits. The brothers' karyotype was unbalanced; they inherited a maternal derivative X chromosome. Deleted distal Xp genes included short-stature homeobox on the X chromosome (SHOX), aryl sulfatase E (ARSE), variably charged X-chromosome mRNA gene A (VCX-A), and steroid sulfatase (STS). The final karyotype was 46,Y,der(X)t(X; Y)(p22.3; q11.2).ish der(X) (DXZ1+, KAL+, STS-, SHOX-) mat. Conclusions: Loss of distal contiguous Xp genes resulted in a syndrome comprising bony deformities, ichthyosis, attention problems, and generalized epilepsy. Candidate epilepsy genes within the deleted segment, such as ASMT, a gene involved in the final synthesis of melatonin, are discussed. Cytogenetic analyses should be included in the clinical evaluation of patients with generalized epilepsy and complex phenotypes. [source]

CMTX: heterozygosity for a GJB1/CX32 mutation in a XXY male results in a mild phenotype

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004
M Milani
Mutations in the GJB1/Cx32 gene (Xq13.1) cause the most common X-linked form of CMT (CMTX1) and are the most frequent cause of CMT disease after the CMT1A duplication. The disorder is characterized by a moderate-to-severe neuropathy in affected males and mild-to-no symptoms in carrier females. We report here a CMT1A-negative family in which 4 females and 2 males were affected, exhibiting different disease severity. Molecular analysis of the GJB1/Cx32 gene uncovered a nonsense mutation (Arg22stop) in exon 2. The mutation, which had been previously described by others and observed by us in numerous other families, occurred in heterozygous form in the 4 females. However, while one of the two male patients was severely affected and shown to be hemizygous, as expected, the other was mildly affected and found to carry the mutation in heterozygous form. Genotyping at the SRY (Yp11.3) and DMD (Xp21) loci suggested the occurrence of the XXY genotype associated with Klinefelter syndrome. Microsatellite analysis indicated that the nondysjunctional error was of paternal origin, as it is usually observed in about half the cases. The patient had no children. At clinical examination, he exhibited a very mild neurologic phenotype and showed signs of hypogonadism (mild gynecomastia and small testes) as well as moderate cognitive impairment. Electrophysiologic, cytogenetic and endocrinologic investigations are in progress in order to define the unusual phenotype in this patient. [source]

Salmonella enterica phage-resistant mutant colonies display an unusual phenotype in the presence of phage Felix 01

LETTERS IN APPLIED MICROBIOLOGY, Issue 6 2007
G. O'Flynn
Abstract Aims:, To investigate irregular colony morphology formation in Salmonella enterica serovar Typhimurium DPC6046 in the presence of a lytic phage, Felix 01. Methods and Results:, Phage-resistant derivatives of the parent strain DPC6046 were isolated which exhibited an irregular colony morphology. These were subjected to viability studies by using confocal scanning laser microscopy and live/dead BacLight stain to evaluate the cell viability within the colony. The phenomenon was also observed with other S. enterica serotypes tested which were normally sensitive to phage Felix. In the case of strain DPC6046, dead cells were clearly evident at the irregular edges of the phage-resistant colonies in locations where the cell density was lower. This colony morphology was not apparent with two other Salmonella phages tested. Conclusions:, These findings support the hypothesis that the unusual morphology is due to reversion to phage sensitivity and consequent cell death within the colony as it forms. Significance and Impact of the Study:, The irregular colony morphology observed is peculiar to phage Felix. The confocal scanning laser microscopy methodology allowed the basis for the irregular morphology to be elucidated. [source]

Pharmacological screening of bryophyte extracts that inhibit growth and induce abnormal phenotypes in human HeLa cancer cells

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2009
Lucie Krzaczkowski
Abstract Antitumor activities of substances from natural sources apart from vascular plants and micro-organisms have been poorly investigated. Here we report on a pharmacological screening of a bryophyte extract library using a phenotypic cell-based assay revealing microtubules, centrosomes and DNA. Among the 219 moss extracts tested, we identified 41 extracts acting on cell division with various combinations of significant effects on interphasic and mitotic cells. Seven extracts were further studied using a cell viability assay, cell cycle analysis and the phenotypic assay. Three distinct pharmacological patterns were identified including two unusual phenotypes. [source]