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Byung-Ok Choi, Sung Hee Kang,
Young Se Hyun,
Sumaria Kanwal,
Sun Wha Park,
Heasoo Koo,
Sang-Beom Kim,
Young-Chul Choi,
Jeong Hyun Yoo,
Jong-Won Kim,
Kee Duk Park,
Kyoung-Gyu Choi,
Song Ja Kim,
Stephan Züchner,
Ki Wha Chung
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ABSTRACT: Both peripheral neuropathy and distal myopathy are well-established inherited neuromuscular disorders characterized by progressive weakness and atrophy of the distal limb muscles. A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss was diagnosed in a large autosomal dominant Korean family. A high density single nucleotide polymorphism (SNP)-based linkage study mapped the underlying gene to a region on chromosome 19q13.3. The maximum multipoint LOD score was 3.794. Sequencing of 34 positional candidate genes in the segregating haplotype revealed a novel c.2822G>T (p.Arg941Leu) mutation in the gene MYH14, which encodes the nonmuscle myosin heavy chain 14. Clinically we observed a sequential pattern of the onset of muscle weakness starting from the anterior to the posterior leg muscle compartments followed by involvement of intrinsic hand and proximal muscles. The hearing loss and hoarseness followed the onset of distal muscle weakness. Histopathologic and electrodiagnostic studies revealed both chronic neuropathic and myopathic features in the affected patients. Although mutations in MYH14 have been shown to cause nonsyndromic autosomal dominant hearing loss (DFNA4), the peripheral neuropathy, myopathy, and hoarseness have not been associated with MYH14. Therefore, we suggest that the identified mutation in MYH14 significantly expands the phenotypic spectrum of this gene.
Human Mutation 06/2011; 32(6):669-77. · 5.69 Impact Factor
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ABSTRACT: Monoclonal antibodies (mAbs) recognizing Class III epitope of CD34 are essential for flow cytometric diagnosis of leukemia.
27H2 mAb was developed from a mouse alternatively immunized with human acute leukemia cell lines, KG1 and Molm-1. Using flow cytometric analysis of various leukemic cell lines and peripheral blood, immunohistochemical study of frozen tonsil, we characterized 27H2 mAb. Antigen immunoprecipitated with 27H2 mAb immunobloted with anti-CD34 mAb. A case of bone marrow sample of acute lymphoblastic leukemia (ALL) patient was obtained at CBNU Hospital. For epitope identification enzyme treatment with neuraminidase and O-sialoglycoprotein endopeptidase (OSGE) and blocking assay with known classIII mAb (HPCA-2) were done.
Only KG1 and Molm-1 revealed positive immunoreactivity. Immunohistochemical staining disclosed strong membranous immunoreactivity on high endothelial venules. Antigen immunoprecipitated by 27H2 mAb showed approximately 100 kDa sized band immunoblotted with anti-CD34 under non-reducing conditions. Epitope recognized by 27H2 mAb disclosed resistancy to both neuraminidase and OSGE treatment and completely blocked with known class III mAb preincubation. CD34 positive leukemic cells in BM of pre B cell ALL patient detected by FITC-conjugated 27H2 and HPCA-2 were identified with similar sensitivity.
A novel murine mAb recognizing class III epitope of human CD34 with high affinity, which is useful for flow cytometric diagnosis of leukemia, was developed.
Immune Network 12/2010; 10(6):239-46.
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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
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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
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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
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ABSTRACT: The clinical value of real-time 3-dimensional echocardiography assessments of left atrial volume in patients with left ventricular dysfunction has not been determined.
Real-time 3-dimensional echocardiography and 2-dimensional Doppler echocardiography were performed on the same day in 108 patients with severe left ventricular dysfunction and in sinus rhythm. End-systolic left atrial volumes were measured using real-time 3-dimensional echocardiography images (LAV-3D) and end-systolic left atrial volumes were calculated by the biplane area-length formula using 2-dimensional echocardiography (LAV-2D). Patients were observed clinically over 10 +/- 7 months.
LAV-2D showed excellent correlation with LAV-3D (r = 0.88, P < .001), but the former was significantly smaller than the latter (-12 +/- 21 mL, P < .001). During follow-up, 31 patients (29%) showed clinical events, including 3 cardiac deaths and 28 hospitalizations as a result of heart failure. Patients with clinical events had larger initial LAV-3D (P < .05) and LAV-2D (P = .05), higher transmitral E velocity, higher E/E' ratio, more severe mitral and tricuspid regurgitation, and higher maximal velocity of tricuspid regurgitation than the 77 patients without events. LAV-3D (P < .001) and age (P < .05) were independent predictors of cardiac events by Cox proportional hazard model, whereas LAV-2D was negatively involved. Patients with initial LAV-3D less than 100 mL had a significantly higher 1-year event-free survival than those with LAV-3D greater than or equal to 100 mL (80 +/- 7 vs 48 +/- 10%, P < .001).
LAV-3D is a major predictor of clinical events in patients with severe left ventricular dysfunction and in sinus rhythm. The clinical value of LAV-3D seems to be superior to that of LAV-2D.
Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 05/2008; 21(5):439-45. · 2.98 Impact Factor
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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
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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
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ABSTRACT: A novel track-and-hold (T&H) employing an operational transconductance amplifier (OTA) with two cross-coupled differential pairs (CCDPs) is proposed for high-accuracy and high-frequency applications. The T&H has a simple architecture requiring smaller capacitors and fewer switches and offers higher speed, lower distortion, and lower power dissipation than its op-amp based counterparts. The chip implemented in 0.18 um CMOS process operates from a single 1.8 V supply and achieves more than 10-bits precision for sampling rate in excess of 120 MS/s.
Integrated Circuits, 2007. ISIC '07. International Symposium on; 10/2007
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ABSTRACT: A novel track-and-hold (T&H) employing an operational transconductance amplifier (OTA) with two cross-coupled differential pairs (CCDPs) is proposed for high-accuracy and high-frequency applications. The T&H has a simple architecture requiring smaller capacitors and fewer switches and offers higher speed, lower distortion, and lower power dissipation than its op-amp based counterparts. The chip implemented in 0.35 um CMOS process operates from a single 1.8 V supply and achieves more than 10-bits precision for sampling rate in excess of 120 MS/s.
Signals, Circuits and Systems, 2007. ISSCS 2007. International Symposium on; 08/2007
