• Journal of Microbiology
• /
• v.35 no.1
• /
• pp.61-65
• /
• 1997

A novel strategy was developed for isolating suppressors from sporulation-deficient mutants. The mutation in the BCY1 gene, which codes for the regulatory subunit of cAMP-dependent protein kinase, when homozygous, results in diploids being meiosis and sporulation deficient. Two plasmids, YCp-MAT.alpha. and YEp-SPOT7-lacZ, were introduced into MAT.alpha. BCY1$\^$+/ or MAT.alpha. bcy1 haploid cells. The transformant of the BCY1$\^$+/ haploid cell produced .betha.-galactosidase under nutrient starvation, but the bcy1 transformant did not. Using this system, the mutagenesis experiment performed on the bcy1 transformant strain resulted in a number of sporulation mutants that produced .betha.-galactosidase under nutrient starvation. One complementation group, sob1, was identified from the isoalted suppressor mutants and characterized as a single recessive mutation by tetrad analysis. Genetic analysis revealed that the sob1 mutation suppressed the sporulation deficiency, the failure to arrest at the G1 phase of the cell cecle, and the sensitivity to heat or nitrogen starvation caused by the bcy1 mutation. However, the sob1 mutation did not suppress the sporulation deficiency of ime1 and of ime2 diploids. These results suggest that the sob1 mutation affects a gene which functions as a downstream regulator in both meiosis and cell cycle regulation.

• Journal of Genetic Medicine
• /
• v.15 no.1
• /
• pp.28-33
• /
• 2018

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by the deficiency of ${\alpha}$-galactosidase A. Patients with classical FD present acroparesthesia, hypohidrosis, cornea verticillata, disseminated angiokeratoma, and microalbuminuria in childhood, and develop life-threatening renal, cardiac, and cerebrovascular complications typically after the fourth decade of life. To date, more than 700 mutations responsible for FD have been identified in the human GLA gene. Herein, we report a novel GLA mutation, c.1117_1141del25 (p.Gly373Profs*10), identified in an 11-year-old Korean boy with FD presenting early cardiac and neurologic manifestation and in other affected family members. The boy had acroparesthesia, hypohidrosis, cornea verticillata, and left ventricular hypertrophy. His mother and sister also had acroparesthesia. Two males on the mother's side had similar pain and died of unknown causes. The plasma ${\alpha}$-galactosidase A activity (4.1 nmol/hr/mg protein) of the patient was markedly lower than the mean value of the controls. The plasma level of globotriaosylsphingosine was elevated in the patient and all the carriers. We concluded the novel GLA mutation c.1117_1141del25 is a pathogenic mutation for FD, probably related to the early cardiac manifestation of FD.

• Clinical and Experimental Pediatrics
• /
• v.53 no.2
• /
• pp.235-238
• /
• 2010

Fabry disease is a rare, X-linked inborn error of glycosphingolipid catabolism caused by a mutation in the gene encoding the ${\alpha}-galactosidase$ A (GLA) enzyme. We report two cases of Fabry disease in a 12-year-old boy who had acroparesthesia and in his elder brother with milder symptoms who were diagnosed by GLA activity assays and the presence of the GLA gene mutation.

• Proceedings of the Zoological Society Korea Conference
• /
• 1997.10b
• /
• pp.261.1-261
• /
• 1997

No Abstract, See Full Text

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.14 no.2
• /
• pp.135-141
• /
• 2014

Objectives: Fabry disease (FD) is a lysosomal storage disease caused by the inappropriate accumulation of globotriaosylceramide (Gb3) in tissues due to a deficiency in the enzyme ${\alpha}$-galactosidase A. Hypertrophic cardiomyopathy is one of the chronic complications of FD. We tried to evaluate the prevalence of Fabry disease in the Korean patients with left ventricular hypertrophy (LVH). Methods: A total of 257 patients with LVH were recruited and they were 172 males (mean 56 years, range 30-81 years) and 84 females (mean 66 years, range 45-85 years). Urinary Gb3 was used to screen FD by high performance liquid chromatography-tandem mass spectrometry. Confirmatory tests were done by alpha-galactosidaseA activity using fluorometric assay and by GLA mutation analysis using sequencing. Results: Four patients were screening positive by urinary Gb3 analysis (cutoff, 25 ug/mmol creatinine). But, one female patient was diagnosed with FD confirmed by enzyme analysis in leukocytes as well as by genetic analysis (1/257 patients, 0.4%). She showed 54.3 ug/mmoL creatinine of Gb3 and 15.5 nmole/hr/mg protein (reference range, $55.2{\pm}12.7nmole/hr/mg$ protein) of alphagalactosidase A activity. And she had a heterozygous GLA mutation of c.796G>A (p.D266N). Her daughter was found to be a carrier for FD confirmed by GLA mutation analysis. Asymptomatic carrier showed 25.5ug/mmol creatinine of Gb3 and 42.5 nmole/hr/mg protein (reference range, $55.2{\pm}12.7nmole/hr/mg$ protein) of alpha-galactosidase A activity. Conclusions: The prevalence of FD in Koran patients with LVH was detected as 0.4%. Although the prevalence seems to be low, screening studies are of great importance for detecting hidden cases as well as for identifying other effected family members.

• Childhood Kidney Diseases
• /
• v.20 no.2
• /
• pp.79-82
• /
• 2016

Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme ${\alpha}-galactosidase$ A, resulting in the accumulation of glycosphingolipids within the lysosomes of various cell types. It has a wide spectrum of clinical phenotypes, and renal failure is a serious complication. Fabry disease is confirmed either by measurement of ${\alpha}-galactosidase$ A activity or by genetic testing for GLA mutations. Renal biopsy findings on light microscopy, specifically enlarged podocytes with foamy cytoplasm, and osmiophilic inclusion bodies in the cytoplasm in all types of renal cells on electron microscopy, are characteristic of this disease. The predominant differential diagnosis is iatrogenic phospholipidosis in association with certain drugs that can cause cellular injuries indistinguishable from Fabry disease. Here, we report the case of a 10-year-old boy with microscopic hematuria who underwent a renal biopsy that showed morphological findings consistent with Fabry disease, although the patient had neither a GLA mutation nor a history of drug consumption. Six years later, spontaneous regression of this renal pathology was observed in a second renal biopsy examination.

• The Korean Journal of Pain
• /
• v.23 no.3
• /
• pp.207-210
• /
• 2010

Fabry disease is an X-linked lysosomal disease caused by deficiency of ${\alpha}$-galactosidase, in which early diagnosis may be missed due to the wide variety of clinical symptoms presenting during disease progression. A 13 year-old boy visited our pain clinic complaining of pricking and burning pain in the toe tips of both feet. Continuous epidural infusion for pain management was performed because of oral analgesics ineffectiveness. The patient underwent ${\alpha}$-galactosidase A (GLA) enzyme analysis based on the clinical impression of Fabry disease from pain with a peripheral neuropathic component and history of anhidrosis. He was diagnosed with Fabry disease after confirming mutation of the GLA gene through a screening test of GLA activity. Enzyme replacement therapy was initiated and pain was tolerated with oral analgesics.

• YAKHAK HOEJI
• /
• v.55 no.1
• /
• pp.56-63
• /
• 2011

Fabry disease (FD) is an X-linked inborn error of glycoshpingolipid metabolism resulting from mutation in the enzyme ${\alpha}$-galactosidase A gene. The disease is an X-linked lipid storage disorder and the lack of ${\alpha}$-Gal A causes an intracellular accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb-3). Measurement of Gb-3 in plasma has clinical importance for monitoring after enzyme replacement therapy for confirmed FD patients. Using electrospray ionization MS/MS we had developed, a simple, rapid, and highly sensitive analytical method for Gb-3 in plasma was used for the purpose of screening FD among high risk groups in Korean population. To date, no comprehensive results for FD screening have been performed and reported in Korea. We screened 1,100 outpatients from 13 hospitals (including clinics) to assess the incidence of FD among patients in high risk groups. For patients with borderline level amount of Gb-3, we repeated Gb-3 or performing complementary or confirmative assay with ${\alpha}$-Gal A activity and DNA mutaion analysis for confirmation diagnosis. Of 1,100 we diagnosed 3 FD with 2 classical type and 1 carrier (0.27%).

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.17 no.3
• /
• pp.92-95
• /
• 2017

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by an ${\alpha}$-galactosidase A (GLA, MIM 300644) enzyme deficiency due to pathogenic variants in the ${\alpha}$-galactosidase A gene (GLA). The disease leads to accumulation of globotriaosylceramide (Gb3) and related glycophospholipids affecting nearly all major organ systems, with the primary sites damaged by Gb3 including renal glomeruli, myocardium, neurons of the dorsal ganglion and autonomic nervous system, and vascular endothelial and smooth muscle. Progressive deposition in these organ systems present with various clinical manifestations including acroparesthesia, renal failure and heart failure. Here, we report a Chinese male diagnosed with Fabry disease in his late $4^{th}$ decades showing improvement of acroparesthesia during enzyme replacement therapy (ERT). A 48-year-old Chinese man who presented with chronic recurrent severe burning pain in his fingers and toes since the age of 10, with worse involvement of the former visited to our clinic for further evaluation. His medical history included a transient ischemic attack aged 40 and diagnosed with stage 4-5 chronic kidney disease aged 47. In the family history, the patient's brother was found to be have Fabry disease 1 month before his visit. Except for his brother, all other members of the family are healthy. Based on his medical history and family history, he was strongly suspicious for Fabry disease. He was found to have a galactose-alpha-1,3-galactose level 4.96 (Reference range, 42.5-67.9) suggestive of Fabry disease. The followed sequencing of GLA coding region in our patient revealed hemizyosity for the mutation c.988C>T (Q330X) in Exon 7. Since ERT start, he showed significant improvement in his symptoms of burning sensation of fingers and toes. On the contrary, due to deteriorating kidney function even with ERT, he is considered for kidney transplantation. Despite of diagnostic delay until late 4th decades, ERT showed a potential improvement of acroparesthesia in our patient. However, late start of ERT can lead to poor outcome in multiorgan function. Therefore, early diagnosis with high index of suspicion followed by continuous ERT with regular monitoring have an impact on quality of life in Fabry disease.

• Molecules and Cells
• /
• v.37 no.8
• /
• pp.620-627
• /
• 2014

We have previously shown that microRNAs (miRNAs) miR-760, miR-186, miR-337-3p, and miR-216b stimulate premature senescence through protein kinase CK2 (CK2) downregulation in human colon cancer cells. Here, we examined whether these four miRNAs are involved in the replicative senescence of human lung fibroblast IMR-90 cells. miR-760 and miR-186 were significantly upregulated in replicatively senescent IMR-90 cells, and their joint action with both miR-337-3p and miR-216b was necessary for efficient downregulation of the ${\alpha}$ subunit of CK2 ($CK2{\alpha}$) in IMR-90 cells. A mutation in any of the four miRNA-binding sequences within the $CK2{\alpha}3^{\prime}$-untranslated region (UTR) indicated that all four miRNAs should simultaneously bind to the target sites for $CK2{\alpha}$ downregulation. The four miRNAs increased senescence-associated ${\beta}$-galactosidase (SA-${\beta}$-gal) staining, p53 and $p21^{Cip1/WAF1}$ expression, and reactive oxygen species (ROS) production in proliferating IMR-90 cells. $CK2{\alpha}$ overexpression almost abolished this event. Taken together, the present results suggest that the upregulation of miR-760 and miR-186 is associated with replicative senescence in human lung fibroblast cells, and their cooperative action with miR-337-3p and miR-216b may induce replicative senescence through $CK2{\alpha}$ downregulation-dependent ROS generation.