-
[show abstract]
[hide abstract]
ABSTRACT: Both the myotonic dystrophy type 1 (DM1) and the X-linked dominant Charcot-Marie-Tooth disease (CMTX1) are well-established inherited neuromuscular disorders characterized by progressive weakness and atrophy of the distal limb muscles. The underlying causes of the DM1 and CMTX1 are mutations in the DMPK and GJB1 gene, respectively. A patient with both DM1 and CMTX1 inherited these from his father and mother, respectively. Histopathological and electrodiagnostic studies revealed both chronic neuropathic and myopathic features. Physical disabilities were more severe than seen with either DM1 or CMTX1 alone. In addition, the present case reveals an asymmetric atrophy (22%) of the right calf muscle compared to the left side.
Neurogenetics 05/2010; 11(4):425-33. · 3.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Charcot-Marie-Tooth disease (CMT) is classified into demyelinating neuropathy (CMT1) and axonal neuropathy (CMT2). Mutations
in the neurofilament light chain polypeptide (NEFL) gene are present in CMT2E and CMT1F neuropathies. Two types of Pro22 mutations have been previously reported: Pro22Ser in
CMT2E with giant axons, and Pro22Thr in CMT1F. In this study, we identified another Pro22 mutation, Pro22Arg, in a Korean
CMT1 family. An investigation to identify the clinical and pathological characteristics of the Pro22Arg revealed that it is
associated with demyelinating neuropathy features in CMT1F. Histopathological findings showed onion bulb formations but no
giant axons. It appears that the Pro22 mutations may influence not only the Thr-Pro phosphorylation site by proline-directed
protein kinases but also other structural alteration of the NEFL protein in a different way.
Journal of Human Genetics 09/2008; 53(10):936-940. · 2.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Distal hereditary motor neuropathy (dHMN) is a heterogeneous disorder characterized by degeneration of motor nerves in the absence of sensory abnormalities. Recently, mutations in the small heat shock protein 27 (HSP27) gene were found to cause dHMN type II or Charcot-Marie-Tooth disease type 2F (CMT2F). The authors studied 151 Korean axonal CMT or dHMN families, and found a large Korean dHMN type II family with the Ser135Phe mutation in HSP27. This mutation was inherited in an autosomal dominant manner, and was well associated with familial members with the dHMN phenotype. This mutation site is located in the alpha-crystallin domain and is highly conserved between different species. The frequency of this HSP27 mutation in Koreans was 0.6%. Magnetic resonance imaging analysis revealed that fatty infiltrations tended to progressively extend distal to proximal muscles in lower extremities. In addition, fatty infiltrations in thigh muscles progressed to affect posterior and anterior compartments but to lesser extents in medial compartment, which differs from CMT1A patients presenting with severe involvements of posterior and medial compartments but less involvement of anterior compartment. The authors describe the clinical and neuroimaging findings of the first Korean dHMN patients with the HSP27 Ser135Phe mutation. To our knowledge, this is the first report of the neuroimaging findings of dHMN type II.
Experimental and Molecular Medicine 07/2008; 40(3):304-12. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous mitochondrial disorder with variable clinical symptoms. Here, from the sequencing of the entire mitochondrial genome, we report a Korean MELAS family harboring two homoplasmic missense mutations, which were reported 9957T>C (Phe251Leu) transition mutation in the cytochrome c oxidase subunit 3 (COX3) gene and a novel 13849A>C (Asn505His) transversion mutation in the NADH dehydrogenase subunit 5 (ND5) gene. Neither of these mutations was found in 205 normal controls. Both mutations were identified from the proband and his mother, but not his father. The patients showed cataract symptom in addition to MELAS phenotype. We believe that the 9957T>C mutation is pathogenic, however, the 13849A>C mutation is of unclear significance. It is likely that the 13849A>C mutation might function as the secondary mutation which increase the expressivity of overlapping phenotypes of MELAS and cataract. This study also demonstrates the importance of full sequencing of mtDNA for the molecular genetic understanding of mitochondrial disorders.
Experimental and Molecular Medicine 06/2008; 40(3):354-60. · 2.48 Impact Factor
-
Ki Wha Chung,
Seung Min Kim,
Il Nam Sunwoo, Sun Young Cho,
Su Jin Hwang,
Joonki Kim,
Sung Hee Kang,
Kee-Duk Park,
Kyoung-Gyu Choi,
Il Saing Choi,
Byung-Ok Choi
[show abstract]
[hide abstract]
ABSTRACT: A wide range of phenotypes have been reported in autosomal recessive (AR) Charcot-Marie-Tooth disease (CMT) patients carrying mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene, such as axonal, demyelinating, and intermediate forms of AR CMT. There have been very few reports of GDAP1 mutations in autosomal dominant (AD) CMT. Here, we report an AD CMT family with a novel Q218E mutation in the GDAP1 gene. The mutation was located within the well-conserved glutathione S-transferase (GST) core region and co-segregated with the affected members in the pedigree. The affected AD CMT individuals had a later disease onset and much milder phenotypes than the AR CMT patients, and the histopathologic examination revealed both axonal degeneration and demyelination.
Journal of Human Genetics 02/2008; 53(4):360-4. · 2.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Moderately elevated plasma homocysteine level is associated with an increased risk of Alzheimer's disease. Thymidylate synthase (TYMS) and 5,10-methylenetetrahydrofolate reductase (MTHFR) are involved in the homocysteine metabolic pathway. In this study, we tried to find the association between TYMS tandem repeat polymorphism and Alzheimer's disease. We analyzed the genotype of the TYMS and MTHFR C677T polymorphisms in 68 Alzheimer's patients and 413 healthy controls. The mean plasma homocysteine level was higher in Alzheimer's disease patients than in healthy controls (p < 0.05). Those subjects who carried at least one TYMS 2R allele [2R(+)] showed an increased risk of Alzheimer's disease (AOR, 2.09; 95%CI, 1.21-4.25). However, the MTHFR C677T polymorphism was not associated with an increased risk of Alzheimer's disease. In the comparison of the combinations of polymorphisms, the risk of Alzheimer's disease was highest in the subjects with the [2R(+)/T(+)] combined genotypes (AOR, 2.76; 95%CI, 1.30-6.71). In conclusion, particular genotype of TYMS tandem repeat polymorphism and combined genotypes of the TYMS tandem repeat and MTHFR C677T polymorphisms appeared to be predictive genetic biomarkers for the risk of Alzheimer's disease.
Korean J. Genetics The Genetics Society of Korea. 10/2007; 29:323-330.
-
[show abstract]
[hide abstract]
ABSTRACT: Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with duplication of chromosome 17p11.2-p12, whereas hereditary neuropathy with liability to pressure palsies (HNPP), which is an autosomal dominant neuropathy showing characteristics of recurrent pressure palsies, is associated with 17p11.2-p12 deletion. An altered gene dosage of PMP22 is believed to the main cause underlying the CMT1A and HNPP phenotypes. Although CMT1A and HNPP are associated with the same locus, there has been no report of these two mutations within a single family. We report a rare family harboring CMT1A duplication and HNPP deletion.
Journal of Clinical Neurology 07/2007; 3(2):101-4. · 1.69 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In an earlier study, a site directed mutant rFVIII (rFVIII(m), Arg(336) --> Gln(336)) expressed in baculovirus-insect cell (Sf9) system was found to sustain high level activity during incubation at 37 degrees celsius for 24 h while the cofactor activity of normal plasma was declined steadily. In this study, a mutant B-domain deleted rFVIII(m), Arg(336) --> Gln(336) expressed in baculovirus-insect cell (Sf9) system was characterized for its enzymatic and chemical properties. The expressed rFVIII(m) and plasma FVIII (pFVIII) were purified by immunoaffinity column chromatography and identified by Western blot analysis. The partially purified rFVIII(m) exhibited cofactor specific activity of 2.01 x 10(3)units/mg protein. The molecular weight of rFVIII(m) ranged between 40 to 150 kDa with a major band at 150 kDa. Treatment of both rFVIII(m) and pFVIII with thrombin increased their cofactor activity in a similar pattern. Treatment of both the activated rFVIII(m) and native FVIII with APC decreased their cofactor activities, however, the former exhibited a slower decrease than the latter, although no significant difference was present. rFVIII(m) formed a complex with vWF, resulting in a stabilized form, and the lag period of thrombin-mediated activating was extended by vWF association. These results implicated that rFVIII(m) expressed in baculovirus-insect cell system had a comparable capacity as FVIII cofactor activity and might be a good candidate for the FVIII replacement therapy for hemophilia A patients.
Experimental and Molecular Medicine 08/2002; 34(3):233-8. · 2.48 Impact Factor
