1.A familial case with brachydactyly type C with a GDF5 mutation.
Hye Ryun YEH ; Beom Hee LEE ; Ja Hye KIM ; Ja Hyang CHO ; Gu Hwan KIM ; Jae Min KIM ; In Hee CHOI ; Han Wook YOO
Journal of Genetic Medicine 2014;11(1):27-30
Brachydactyly type C is a limb malformation characterized by shortening of the second, third, and fifth middle and/or proximal phalanges, but it has variable phenotypic expressivity. Mutations in the growth differentiation factor-5 (GDF5) gene cause isolated brachydactyly C. Herein, we report a familial case with isolated brachydactyly type C characterized by brachymesophalangy of both second and third digits, with a GDF5 missense mutation, and discuss the phenotypic variability of the condition. Identifying more cases with genetic confirmation will help elucidate the clinical and genetic characteristics of this condition in the Korean population.
Brachydactyly*
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Extremities
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Mutation, Missense
3.Identification of a New Selective Chemical Inhibitor of Mutant Isocitrate Dehydrogenase-1.
Hyo Joon KIM ; Bu Young CHOI ; Young Sam KEUM
Journal of Cancer Prevention 2015;20(1):78-83
BACKGROUND: Recent genome-wide sequencing studies have identified unexpected genetic alterations in cancer. In particular, missense mutations in isocitrate dehydrogenase-1 (IDH1) at arginine 132, mostly substituted into histidine (IDH1-R132H) were observed to frequently occur in glioma patients. METHODS: We have purified recombinant IDH1 and IDH1-R132H proteins and monitored their catalytic activities. In parallel experiments, we have attempted to find new selective IDH1-R132H chemical inhibitor(s) from a fragment-based chemical library. RESULTS: We have found that IDH1, but not IDH1-R132H, can catalyze the conversion of isocitrate into alpha-ketoglutarate (alpha-KG). In addition, we have observed that IDH1-R132H was more efficient than IDH1 in converting alpha-KG into (R)-2-hydroxyglutarate (R-2HG). Moreover, we have identified a new hit molecule, e.g., 2-(3-trifluoromethylphenyl)isothioazol-3(2H)-one as a new selective IDH1-R132H inhibitor. CONCLUSIONS: We have observed an underlying biochemical mechanism explaining how a heterozygous IDH1 mutation contributes to the generation of R-2HG and increases cellular histone H3 trimethylation levels. We have also identified a novel selective IDH1-R132H chemical hit molecule, e.g., 2-(3-trifluoromethylphenyl)isothioazol-3(2H)-one, which could be used for a future lead development against IDH1-R132H.
Arginine
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Glioma
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Histidine
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Histones
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Humans
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Mutation, Missense
4.Identification of two novel variants of the PCCB gene in a pedigree affected with propionic acidemia.
Qigang ZHANG ; Guanglai FAN ; Shu ZHANG ; Yuefang LIU ; Wenjie ZHANG ; Qiong PAN
Chinese Journal of Medical Genetics 2021;38(3):251-254
OBJECTIVE:
To detect pathogenic variants in a pedigree affected with propionic acidemia (PA).
METHODS:
The proband was subjected to high-throughput next-generation sequencing. Suspected variants were validated by Sanger sequencing of his family members. mRNA was extracted from peripheral blood lymphocytes from the proband's father in order to verify the impact of the splicing variant by RT-PCR combined with Sanger sequencing. The pathogenicity of the missense variant was predicted by using PolyPhen-2, Mutation Taster, SIFT, COBALT and HOPE software.
RESULTS:
The proband was found to harbor compound heterozygous variants of the PCCB gene, namely c.184-2A>G and c.733G>A (p.G245S), which were respectively inherited from his father and mother. RT-PCR combined with Sanger sequencing confirmed skipping of exon 2 during transcription. Bioinformatic analysis indicated the c.733G>A (p.G245S) variant to be damaging.
CONCLUSION
The two variants of the PCCB gene probably underlay the disease in this patient. Above findings have enriched the spectrum of PCCB gene variants.
Exons
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Humans
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Mutation
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Mutation, Missense
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Pedigree
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Propionic Acidemia/genetics*
5.The Analysis of LHbeta -subunit Variants in Infertile Patients with Premature Ovarian Failure (POF) in Korea.
Eu Gene LEE ; Nam Keun KIM ; Sook Hwan LEE ; Jung Jae KO ; Kwang Yul CHA ; Hye Sun JEON ; Kyung Ah LEE
Korean Journal of Fertility and Sterility 2000;27(2):179-182
This study was performed to determine whether the LHbeta -subunit gene missense mutation is present in Korean infertile patients with 46,XX POF women. The variants of LHbeta exon 2 (Trp 8Arg; TGG to CGG and Ile15Thr; ATC ti ACC) were studied in forty-four 46.XX idiopathic POF and 54 nonpregnant women. The LHbeta exon 2 variants were more frequent in POF patients (20.5%) than nonpregnant( 16.7%) women (p>0.05). POF patients with the variant was slightly higher than nonpregnant women with the variant.
Exons
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Female
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Humans
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Korea*
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Mutation, Missense
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Primary Ovarian Insufficiency*
6.Molecular variants of the FSH receptor exon 10 (Thr307Ala; A919G) in premature ovarian failure (POF) women by PCR-SSCP.
Nam Keun KIM ; Sook Hwan LEE ; Yoon Sung NAM ; Tae Jong SOHN ; Sang Hee PARK ; Chan PARK ; Jung Jae KO ; Kwang Yul CHA
Korean Journal of Obstetrics and Gynecology 2000;43(7):1144-1146
OBJECTIVE: This study was performed to determine whether the FSH receptor mutation is present in infertile Korean patients with 46,XX premature ovarian failure (POF) women. METHODS: The variant of FSH receptor exon 10 in thirteen 46, XX idiopathic POF and 4 healthy fertile (control) women were studied. Missense mutation in Exon 10 was detected in POF patients and healthy fertile women by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP). RESULTS: The variant types of FSH receptor exon 10 (Thr307Ala; A919G) were found in healthy fertile (control) and POF women. CONCLUSIONS: This mutation may not be specific in POF patients and further study is needed in fertile (control) and POF women.
Exons*
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Female
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Humans
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Mutation, Missense
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Primary Ovarian Insufficiency*
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Receptors, FSH*
7.Quinidine Trial in a Patient with Epilepsy of Infancy with Migrating Focal Seizure and KCNT1 Mutation.
Nalee JEE ; Ara KO ; Se Hee KIM ; Joon Soo LEE ; Heung Dong KIM ; Seung Tae LEE ; Jong Rak CHOI ; Hoon Chul KANG
Journal of the Korean Child Neurology Society 2017;25(3):169-173
Epilepsy of infancy with migrating focal seizure (MFEI) is an early-onset epileptic encephalopathy characterized by randomly migrating focal seizures and psychomotor deterioration. It is associated with mutations in a variety of genes, with potassium sodium-activated channel subfamily T member 1 (KCNT1) being an example. Previously reported KCNT1 mutations in MFEI are gain-of-function mutations. Therefore, quinidine therapy targeted at reduction of pathologically increased KCNT1 channel-mediated potassium conductance has been proposed as a target treatment for MEFI with KCNT1 mutation. The authors report a case involving a patient with MFEI and a missense mutation in KCNT1 (c.7129G>A; p.Phe346Leu) treated with quinidine therapy. Seizure activity was poorly responsive to quinidine.
Brain Diseases
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Epilepsy*
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Humans
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Mutation, Missense
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Potassium
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Quinidine*
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Seizures*
8.Novel KIT Missense Mutation P665S in a Chinese Piebaldism Family.
Yan ZHENG ; Fen LIU ; Yao YANG ; Yanhua LIANG
Annals of Dermatology 2017;29(6):801-803
No abstract available.
Asian Continental Ancestry Group*
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Humans
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Mutation, Missense*
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Piebaldism*
9.Different Subtypes Caused by c.721C>T Substitution in the Exon 7 of ABO Gene.
Jian-Yu XIAO ; Chen-Chen FENG ; Tai-Xiang LIU ; Li-Li SHI ; Ruo-Yang ZHANG ; Cheng-Yin HUANG ; Qing CHEN
Journal of Experimental Hematology 2021;29(6):1917-1922
OBJECTIVE:
To analyze the different subtypes caused by c.721C>T substitution in the exon 7 of the ABO gene, and to investigate the related molecular mechanism of different antigens expression.
METHODS:
ABO subtypes in 7 samples were identified by standard serological methods. The exons 6, 7, and adjacent intron of ABO gene were amplified by Polymerase Chain Reaction (PCR), and the PCR products were analyzed by direct DNA sequencing and cloning sequencing.
RESULTS:
ABO subtypes phenotypes were A
CONCLUSION
c.721C>T substitution in the ABO gene causes p.Arg241Trp exchange resulting in the decreasing of GTA or GTB activities and weaker antigen expression. O.01.07 is a null allele which cannot form a functional catalytic enzyme has no effect on A
ABO Blood-Group System/genetics*
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Alleles
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Exons
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Genotype
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Mutation, Missense
10.Factor VIII Gene Mutations in Korean Patients with Hemophilia A.
Young Min CHOI ; Eun Joo KIM ; Mi Ran LEE ; Young Soo SON ; Jin CHOE ; Doyeong HWANG ; Jong Kwan JUN ; Byung Chul JEE ; Seung Yup KU ; Chang Suk SUH ; Seok Hyun KIM ; Jung Gu KIM ; Shin Yong MOON
Korean Journal of Obstetrics and Gynecology 2004;47(10):1975-1981
OBJECTIVE: To identify mutations within the factor VIII gene in Korean patients with severe hemophilia A. DESIGN: A laboratory analysis. METHODS: We systematically sequenced the promoter, all exons and splice junctions of factor VIII gene in 23 unrelated Korean patients with severe hemophilia A. Patients with factor VIII gene inversion were excluded. RESULTS: Twelve patients (52.2%) showed a point mutation, among which 6 were nonsense mutations and the other 6 were missense mutations. A large deletion was found in 6 (26.1%) patients, a small deletion in 2 (8.7%), a small insertion in one patient. Two patients had compound mutations: one patient had two missense mutations, and the other had a missense mutation and 4 bp insertion. Ten (43.5%) out of 23 mutations found are novel. CONCLUSION: Mutations within the factor VIII gene found in Korean patients with moderate to severe hemophilia A are diverse as expected. And we have found 10 novel mutations. Our results can help understanding the molecular pathology of hemophilia A.
Codon, Nonsense
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Exons
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Factor VIII*
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Hemophilia A*
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Humans
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Mutation, Missense
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Pathology, Molecular
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Point Mutation