scholarly journals A point mutation in the albumin gene in a Chinese patient with familial dysalbuminemic hyperthyroxinemia

1999 ◽  
pp. 374-378 ◽  
Author(s):  
KT Tang ◽  
HJ Yang ◽  
KB Choo ◽  
HD Lin ◽  
SL Fang ◽  
...  
Keyword(s):  
Point Mutation ◽  
Serum Proteins ◽  
Direct Sequencing ◽  
Chinese Patient ◽  
Normal Range ◽  
Step Method ◽  
Japanese Family ◽  
Albumin Gene ◽  
First Case ◽  
Euthyroid Hyperthyroxinemia

Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant disorder characterized by euthyroid hyperthyroxinemia. However, FDH has not been reported in Chinese or African patients. Here, we report the first case of FDH in a Chinese patient. A 69-year-old Chinese man was found to have increased serum total T(4) concentrations (198-242nmol/l; normal range 58-148nmol/l) and free T(4) concentrations (>58pmol/l; T(4) analog method, normal range 9-28pmol/l). Serum total T(3) and TSH concentrations were normal. The patient was misdiagnosed as hyperthyroid and was later suspected to have a TSH-producing tumor by the finding of a pituitary microadenoma, which was eventually proven to be a non-functional pituitary 'incidentaloma'. Electrophoretic analysis of the patient's serum proteins demonstrated enhanced albumin binding of [(125)I]T(4). Serum free T(4) concentrations were normal (16-19pmol/l, normal range 9-26pmol/l) when a two-step method was used. Direct sequencing of the albumin gene showed a guanine to adenosine transition in the second nucleotide of codon 218, resulting in a substitution of histidine (CAC) for the normal arginine (CGC) in one of the two alleles in the patient. The point mutation was further confirmed by HphI digestion of exon 7 of the albumin gene. The patient's son was not affected. Our studies demonstrated that the point mutation of the albumin gene in a Chinese patient with FDH was similar to that found in western white families, but differed from that in a Japanese family in whom a guanine to cytosine transition at the same position was found.

scholarly journals A Novel Point Mutation in the Insulin Gene Giving Rise to Hyperproinsulinemia*

1997 ◽  
Vol 82 (5) ◽  
pp. 1629-1631 ◽  
Author(s):  
Margaret G. Warren-Perry ◽  
Susan E. Manley ◽  
Diane Ostrega ◽  
Ken Polonsky ◽  
Sandra Mussett ◽  
...  
Keyword(s):  
Point Mutation ◽  
Plasma Insulin ◽  
Direct Sequencing ◽  
Insulin Level ◽  
Insulin Gene ◽  
Normal Range ◽  
A Chain ◽  
The Uk ◽  
Processing Protease

Abstract A 58-yr-old obese white Caucasian male type 2 diabetic, entered into the UK Prospective Diabetes Study, was found to have raised fasting total proinsulin levels 708 pmol/L−1 (normal range, 3–16 pmol/L−1) and normal specific plasma insulin level 29 pmol/L−1 (normal range, 21–75 pmol/L−1). Immunoreactive plasma insulin, measured by RIA, was 503 pmol/L−1. DNA was extracted, the insulin gene amplified by the PCR, and by direct sequencing, a novel point mutation, G1552C, was identified, which resulted in the substitution of proline (CCT) for arginine (CGT) at position 65. This prevented cleavage of the C-peptide A-chain dibasic cleavage site (lys-arg) by the processing protease in the pancreatic β-cells. The plasma proinsulin and insulin levels were in accord with expression of both the wild-type and the mutant alleles. The G1552C mutation was not linked with diabetes, because it was present in a 37-yr-old nondiabetic daughter and not in a 35-yr-old daughter who had had gestational diabetes.

Biological Characteristics Op Antithrombin III In An Antithrombin III Deficient Family

1981 ◽  
Author(s):  
S Kondo ◽  
T Matsuo ◽  
Y Ohoki ◽  
O Matsuo
Keyword(s):  
Antithrombin Iii ◽  
Recurrent Thrombosis ◽  
Normal Range ◽  
Japanese Family ◽  
Neutralization Activity ◽  
Normal Value ◽  
Antithrombin Activity ◽  
At Iii ◽  
Molecular Abnormality ◽  
Antifactor Xa

In the familial AT III deficiency of a Japanese family, the propositus (a-39-yr old female) and her mother had episodes of recurrent thrombosis and their AT III levels as measured immunologically and biologically were below the normal value. In the plasma of her brother, the AT III concentration as measured immunologically was half of the normal value, but his biological antithrombin activity was within the normal range. The progressive antithrombin activity and antifactor Xa activity of plasma samples in this familial AT III deficiency were within the normal range. Measurements of the rate of thrombin neutralization activity revealed that the brother’s plasma was in the normal range, but the plasma of the propositus and of her mother showed rates of thrombin neutralization activity which were somewhat below the normal value. The rate of thrombin neutralization activity per mg protein of AT III was highest in the plasma of the brother, and became slower in the mother, propositus, and pooled normal plasma in that order. In the plasma of this familial AT III deficiency, the rate of Xa neutralization activity was much slower than the normal value. It is postulated that since the antithrombin of the brother of the propositus was found to react as normal in the neutralization of thrombin, he does not have episodes of thrombosis. Such characteristic hyperfunction of antithrombin in the plasma of the brother may be due to some molecular abnormality of AT III within this hereditary deficient family.

Detection of protein binding abnormalities in euthyroid hyperthyroxinemia.

1988 ◽  
Vol 34 (9) ◽  
pp. 1745-1748 ◽  
Author(s):  
P M George ◽  
J M Sheat ◽  
B N Palmer
Keyword(s):  
Protein Binding ◽  
Clinical Examination ◽  
Serum Proteins ◽  
Protein Fractions ◽  
Agarose Gel ◽  
Euthyroid Hyperthyroxinemia

Abstract This is a procedure for rapidly identifying the three common abnormalities in binding of thyroxin by protein. After incubation with [125I]thyroxin, serum proteins are separated by electrophoresis on agarose gel and binding of thyroxin to the various protein fractions is determined after autoradiography. Quantitatively abnormal binding to albumin or prealbumin and thyroxin autoantibodies is easily demonstrated by this technique. Normally, less than 6% is bound to albumin, and no binding by prealbumin is detected. In dysalbuminemic hyperthyroxinemia, about 30% of the serum thyroxin is bound to albumin; in prealbumin-associated hyperthyroxinemia, 7% is bound to prealbumin. With this procedure these protein-binding abnormalities can be simply identified, and it may be useful when results of a thyroxin assay are not consistent with results of a sensitive thyrotropin assay or the patient's clinical examination.

scholarly journals Antithrombin-Gly 424 Arg: a novel point mutation responsible for type 1 antithrombin deficiency and neonatal thrombosis

Blood ◽  
1994 ◽  
Vol 83 (1) ◽  
pp. 146-151 ◽  
Author(s):  
K Jochmans ◽  
W Lissens ◽  
R Vervoort ◽  
S Peeters ◽  
M De Waele ◽  
...  
Keyword(s):  
Point Mutation ◽  
Direct Sequencing ◽  
Mutant Gene ◽  
Single Strand Conformation Polymorphism ◽  
Molecular Defect ◽  
Polymorphism Analysis ◽  
Functional Protein ◽  
Antithrombin Deficiency ◽  
Increased Risk

Abstract Inherited type 1 antithrombin (AT) III deficiency is characterized by a decrease of immunoreactive and functional protein levels to about 50%. The disorder is associated with a significantly increased risk of thromboembolism. We have investigated the molecular basis of type 1 AT deficiency in a Belgian family. The diagnosis of the disease was primarily made in a newborn girl with unusually severe thrombotic complications. Using the polymerase chain reaction and single-strand conformation polymorphism analysis, followed by direct sequencing of AT gene fragments, we identified a novel point mutation in exon 6. We detected a G to C substitution in the first position of codon 424 leading to a glycine to arginine substitution. The modification at this highly conserved position in the serine protease inhibitor gene family probably leads to an unstable mutant-gene product. The mutation creates a unique restriction site for the enzyme Hha I in exon 6. This change permitted a rapid and accurate screening of the kindred with identification of the molecular defect in five other family members.

scholarly journals A heterozygous point mutation of the ANKRD11 (c.2579C>T) in a Chinese patient with idiopathic short stature

2019 ◽  
Vol 7 (12) ◽  
Author(s):  
Yabin Kang ◽  
Dongye He ◽  
Yanying Li ◽  
Yanhong Zhang ◽  
Qian Shao ◽  
...  
Keyword(s):  
Short Stature ◽  
Point Mutation ◽  
Chinese Patient ◽  
Idiopathic Short Stature

scholarly journals Molecular defect in coagulation factor XFriuli results from a substitution of serine for proline at position 343

Blood ◽  
1991 ◽  
Vol 77 (2) ◽  
pp. 317-323 ◽  
Author(s):  
HL James ◽  
A Girolami ◽  
DS Fair
Keyword(s):  
Point Mutation ◽  
Serine Proteases ◽  
Direct Sequencing ◽  
Coagulation Factor ◽  
Amino Acid Position ◽  
Molecular Defect ◽  
Nucleotide Position ◽  
Factor X ◽  
Gene Coding ◽  
X Gene

Abstract Our previous findings suggested that coagulation factor XFriuli could be functionally defective owing to a point mutation in the portion of the factor X gene coding for the fully activated heavy chain. To verify the existence of this postulated change, we analyzed all eight exons of the normal and Friuli factor X gene. Each exon was amplified from genomic DNA using the polymerase chain reaction and cloned into the plasmid pUC19. The amplified DNA inserts were subjected to direct sequencing by the dideoxy chain termination method with forward and reverse oligonucleotide sequencing primers. A point mutation (C to T transition at nucleotide position 19,297) that results in coding for serine (TCC) in place of proline (CCC) at amino acid position 343 was found. This substitution involves a highly conserved proline residue oriented spatially close to both the cleavage site of the zymogen and the active site of the enzyme and explains the previous observations of discrete biochemical and functional differences between factor XFriuli and normal factor X. The mutation abolished an HgiCI restriction site present in the normal factor X gene, and this change constitutes the basis for a convenient method for screening individuals carrying this molecular defect. Proline343 is in conserved region 5 of the serine protease superfamily to which factor X belongs and is part of a 14- residue L*****P******C motif that occurs in at least 16 other enzymes. Computer analysis suggests that the motif may be an essential aspect of conformational features important to functional properties of factor X as well as other serine proteases.

scholarly journals Severe Drug-Induced Liver Injury from Combination Encorafenib/Binimetinib

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Nicholas Gravbrot ◽  
Srinath Sundararajan
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Combination Therapy ◽  
Hepatic Injury ◽  
Mek Inhibitor ◽  
New Combination ◽  
Normal Range ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
First Case

Encorafenib/binimetinib is a new combination BRAF/MEK inhibitor used in the treatment of advanced or metastatic BRAFV600-mutant melanoma. Though generally tolerated well, mild to moderate aminotransferase elevations are common. However, significant liver injury has not been demonstrated in the literature. Here, we report the first case of severe hepatic injury associated with encorafenib/binimetinib in a 58-year-old gentleman requiring admission and extensive workup. He was successfully treated by withdrawing the combination therapy, and liver function returned to normal range.

scholarly journals The first case report of McLeod syndrome in a Chinese patient

2013 ◽  
Vol 2013 (aug13 1) ◽  
pp. bcr2013200205-bcr2013200205 ◽  
Author(s):  
B. L. Man ◽  
Y. P. Yuen ◽  
S. F. Yip ◽  
S. H. Ng
Keyword(s):  
Case Report ◽  
Chinese Patient ◽  
First Case

CML Developed in a Japanese Family Transmitting a Novel Point Mutation in the Thrombopoietin Gene(TPO).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4220-4220 ◽  
Author(s):  
Yasuo Oshima ◽  
Norio Komatsu ◽  
Keiya Ozawa ◽  
Akio Fujimura
Keyword(s):  
Point Mutation ◽  
Translational Regulation ◽  
Intron Retention ◽  
Leukemia Virus ◽  
Donor Site ◽  
Exon Skipping ◽  
Myeloproliferative Disorders ◽  
Complete Response ◽  
Japanese Family ◽  
Hematopoietic Stem

Abstract Introduction: Four families are reported to have hereditary thrombocythemia (HT) with a mutation in TPO. Their clinical manifestation is essentially thrombocytosis without leukemia. CML is one of myeloproliferative disorders, and shows leukocytosis and thrombocytosis associated with a proliferation of malignant clone originated from a hematopoietic stem cell (HSC). The incidence of CML is about 5 per 100,000 in Japan. Mutations of cytokine receptor including c-kit, flt-3 and G-CSF receptor are reported as a cause of AML. Especially flt-3 abnormalities are found in about 20% of AML. However, abnormality of c-mpl or TPO is not reported as a cause of leukemia. In this paper, we analyzed a CML case with novel point mutation in the TPO who still had thrombocytosis after cytogenetic complete response. Case: Japanese, 35 y.o., male, complained leukocytosis. He had a family history of thrombocytosis in 4 individuals over 3 generations. A physical examination revealed a moderate splenomegaly. Laboratory tests at the time of diagnosis were as follows; WBC 141,000/μl (blast 1.8%, promyelo 2.4%, myelo 20.0%, meta 8.2%, stab 24.2%, seg 22.2%, immature eosinophils 1.8%, eosinophil 3.6%, immature basophils 0.4%, basophils 10.4%, mono 1.0%, lymphocytes 4.0%, erythroblast 3%), PLT 641,000/μl and NAP score 53 (nl; 156–271). Bone marrow showed hypercellularity with the increased megakaryocytes(Meg), bcr-abl fusion mRNA positive, Ph1 chromosome positive. After 5 months treatment with STI571, most of clinical findings including karyotype and fusion mRNA turned to be normal, but thrombocyte(PLT) still showed more than 1,000,000/μl. At this time, serum TPO concentration was 8.14 f mole/ml (nl; 0.40 +/− 0.28 f mole/ml, mean +/− SD). Genetic analysis of TPO revealed novel point mutation at splicing donor site of 3′-end of the exon3. A point mutation at splicing donor site is reported to cause an exon-skipping and intron-retention, which induce a malfunction of a suppressive post-transcriptional and translational regulation, and consequent high-level expression of functional TPO protein. Discussion: TPO was cloned as a c-mpl ligand, which leads to the production of PLTs. Its receptor is a c-mpl proto-oncogene product, which is expressed not only in Meg, but also in HSC. Thus, TPO can stimulate HSC. The c-mpl transgenic mice are reported to have the increased Meg, its committed progenitor and PLT. Knockout mice of TPO presented not only the decreased Meg, but also multi-lineage committed progenitors. Thus, a modulation of c-mpl or its ligand function affects on both Meg and HSC. The c-mpl was cloned as a cellular homolog of a viral oncogene, v-mpl of myeloproliferative leukemia virus (MPL). The MPL causes myeloproliferative leukemia syndrome through v-mpl function in mice. Since v-mpl and c-mpl indicate high homology, it is possible that abnormal c-mpl function causes v-mpl like response. Through continuous stimulation of c-mpl signal, high TPO concentration may have induced a malignant transformation of HSC or supported a survival of an immature malignant clone in the present case. Improvement of thrombocytosis in CML is one of hematological responses to an anti-CML treatment such as STI571. In such a case who had good response other than thrombocytosis, an existence of HT might be considered. On the other hand, during following up HT family, occurrence of CML should be noted.

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