Clinical characteristics and genetic analysis of gene mutations in a Chinese pedigree with Peutz‐Jeghers syndrome

To investigate the clinical characteristics, auxiliary examination and treatment of Wilson’s disease(WD). The clinical data of a child with WD were summarized and analyzed comprehensively in conjunction with the literature reference. WD is a hereditary disease with a large age span, diverse early symptoms, high misdiagnosis rate, abnormal liver function, decreased ceruloplasmin, increased urinary copper, K-F rings, ATP7B gene mutation, ATP7B gene mutations, and abnormalities in abdominal and cranial brain imaging, which can be clearly diagnosed and require lifelong treatment. WD can be diagnosed according to the clinical manifestations and auxiliary examination to reduce misdiagnosis. The timely diagnosis and treatment will improve the prognosis the quality of life.

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Mutational activation of the K-ras oncogene and the effect of chemotherapy in advanced adenocarcinoma of the lung: a prospective study.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.1.285 ◽

1997 ◽

Vol 15 (1) ◽

pp. 285-291 ◽

Cited By ~ 63

Author(s):

S Rodenhuis ◽

L Boerrigter ◽

B Top ◽

R J Slebos ◽

W J Mooi ◽

...

Keyword(s):

Lung Cancer ◽

Clinical Characteristics ◽

Gene Mutations ◽

Close Relative ◽

Ras Gene ◽

Ras Mutation ◽

Ras Mutations ◽

Adenocarcinoma Of The Lung ◽

Response To Chemotherapy ◽

Mutational Activation

PURPOSE To determine whether the clinical course and the response to chemotherapy of patients with advanced adenocarcinoma of the lung depends on the presence or absence of a ras mutation in the tumor. Mutational activation of K-ras is a strong adverse prognostic factor in stage I or II lung cancer and laboratory studies have suggested that ras mutations lead to resistance against ionizing radiation and chemotherapy. PATIENTS AND METHODS Patients with advanced adenocarcinoma of the lung with measurable or assessable disease received chemotherapy with mesna, ifosfamide, carboplatin, and etoposide (MICE). Archival biopsies, fresh biopsies, or fine-needle aspirations were tested for the presence of ras gene mutations. Associations of ras mutations with clinical characteristics, response to chemotherapy, and survival were studied. RESULTS The presence or absence of ras gene mutations could be established in 69 of 83 patients (83%). A total of 261 courses of MICE were administered to 62 informative patients, 16 of whom were shown to have a K-ras mutation-positive tumor. The frequency of mutations (26%) and the type of mutations closely matched the pattern we have previously reported in operable disease. Patients with a ras mutation in their tumor were more likely to have a close relative with lung cancer, but other clinical characteristics, such as pattern of metastases, response, and survival, were similar between the ras mutation-positive and ras mutation-negative groups. CONCLUSION Patients with advanced lung adenocarcinoma who harbor a ras mutation may have major responses to chemotherapy and have similar progression-free and overall survival as patients with ras mutation-negative tumors. K-ras mutations may represent one of several ways in which early tumors are enabled to metastasize to distant sites.

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Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death?

Journal of Molecular Medicine ◽

10.1007/s00109-004-0589-1 ◽

2004 ◽

Vol 83 (1) ◽

pp. 79-83 ◽

Cited By ~ 285

Author(s):

Jop H. van Berlo ◽

Willem G. de Voogt ◽

Anneke J. van der Kooi ◽

J. Peter van Tintelen ◽

Gisèle Bonne ◽

...

Keyword(s):

High Risk ◽

Sudden Death ◽

Clinical Characteristics ◽

Meta Analysis ◽

Gene Mutations ◽

Lamin A ◽

Lmna Gene

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Clinical characteristics of spectrum of GNE gene mutations in Reunion-Island cohort.

Neuromuscular Disorders ◽

10.1016/j.nmd.2017.06.203 ◽

2017 ◽

Vol 27 ◽

pp. S148-S149

Author(s):

I. Grigorashvili-Coin ◽

M. Campech ◽

F. Darcel ◽

M. Jacquemont ◽

M. Kranh ◽

...

Keyword(s):

Clinical Characteristics ◽

Gene Mutations ◽

Reunion Island ◽

Réunion Island ◽

Gne Gene

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Mutation analysis of the STK11/LKB1 gene and clinical characteristics of an Australian series of Peutz-Jeghers syndrome patients

Clinical Genetics ◽

10.1034/j.1399-0004.2002.620405.x ◽

2002 ◽

Vol 62 (4) ◽

pp. 282-287 ◽

Cited By ~ 38

Author(s):

RJ Scott ◽

R Crooks ◽

CJ Meldrum ◽

L Thomas ◽

CJA Smith ◽

...

Keyword(s):

Mutation Analysis ◽

Clinical Characteristics ◽

Peutz Jeghers Syndrome

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Clinical Charactistics of Ph-Negative MPN Patients with Coexistence of JAK2V617F, Calr and MPL Mutation

Blood ◽

10.1182/blood-2020-142096 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 27-28

Author(s):

Dan Ma ◽

Ping Liu ◽

Chengyun Pan ◽

Bingqing Cheng ◽

Yaming Zhang ◽

...

Keyword(s):

Clinical Characteristics ◽

Conflicts Of Interest ◽

Gene Mutations ◽

Interferon Α ◽

Driver Gene ◽

Fisher Exact Test ◽

Single Mutation ◽

Double Mutation ◽

Mutation Carriers ◽

Pubmed Database

Background and purpose: JAK2, CALR and MPL gene mutations are the driver genes leading to the pathogenesis of ph-negative myeloproliferative meoplasm (MPN). However, it's still unkonwn about the effect of double gene mutations coexisting in ph-negative MPN patients. In this study, we analyzed the clinical significance of the three driver gene mutations when they coexisted in patients with MPN. Methods: Collected bone marrow or peripheral blood samples of 221 patients with suspected MPN who were in the Affiliated Hospital of Guizhou Medical University between May 2017 and April 2020; qPCR detection for JAK2V617F mutation and sanger sequencing detection for CALR gene exon 9 and MPL Exon 10 mutation. Searched Pubmed database related to the coexistence of the three driver gene mutations and extracted information; Fisher exact test to analyze the differences in clinical characteristics between double mutation carriers and single mutation carriers. Shapiro-Wilk statistical analysis of the differences in clinical characteristics of ET patients with different types of double mutations. Results: 1 ET and 1 PMF patient carried both JAK2V617F and CALR gene mutations were found in our center, accounting for 0.9% of ph-negative MPN. The CALR carried by PMF patients was a newly discovered mutation type, c.1126_1127insTTTGC, R376Lfs*56. Through database search, we collected 26 literatures involving MPN case reports with double-driver gene mutations. By fitting analysis with the clinical information of positive patients in our center, a total of 74 MPN patients were collected, of which the number of ET patients was the largest(57/74, accounting for 77.03%). The most common coexisting mutant type was JAK2V617F plus CALR (63/74, 85.14%). The age of onset of MPN patients with double-driver gene mutations was significantly higher than that of single-mutation carriers, and the proportion of patients over 70 years of age was higher (p<0.05), and double mutation carriers had higher platelet count levels(Plt) (p<0.05). The proportion of patients with splenomegalia was lower (p<0.05). The clinical characteristics of ET patients were similar to MPN patients, but no difference in the incidence of splenomegalia (p>0.05). Among PMF patients, the Plt and the proportion of patients with megasplenomegaly in double mutation carriers were similar to those in MPN patients, but the hemoglobin(Hb) was higher (p<0.05). In addition, we also compared the clinical characteristics of ET patients with different gene mutation types. The results showed that the Hb of patients with JAK2V617F and CALR mutations were higher than those of ET patients with JAK2V617F and MPL mutations (p<0.05), but the Plt level is low (p<0.05). Although there were no significant differences in age, gender, IPSET-thrombosis and IPSET (IWG-MRT) scores and WBC between the two groups, the proportion of female ET patients with JAKV617F with MPL mutation was significantly higher than that of JAK2V617F with CALR mutation group (p<0.05). And the proportion of patients with WBC exceeding 11×109/L was also higher (p<0.05). In addition, only one PV patient carried JAK2V617F and CALR, and achieved partial or complete remission after treatment with standard treatment regimens (hydroxyurea or interferon-α). Conclusion: JAK2V617F, CALR and MPL gene mutations are not mutually exclusive in MPN patients, but a certain number of double mutation carriers are ignored. Compared with patients with single-gene mutations, patients with double-gene mutations are older and have higher platelet counts, and should be treated differently in later treatment. At the same time, there are also differences between ET patients with different mutation combinations. These results suggest that it is very necessary for MPN patients to check for three driver gene mutations at the same time, and this type of patients may become a new subtype of MPN. Disclosures No relevant conflicts of interest to declare.

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Epidemiological and Genetic Analysis of Sideroblastic Anemia — Multicenter Study In Japan

Blood ◽

10.1182/blood.v116.21.4225.4225 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4225-4225

Author(s):

Rie Ohba ◽

Kazumichi Furuyama ◽

Shigeru Tsuchiya ◽

Atsushi Manabe ◽

Etsuro Ito ◽

...

Keyword(s):

Bone Marrow ◽

Genetic Analysis ◽

Conflicts Of Interest ◽

Age Of Onset ◽

Gene Mutations ◽

Clinical Information ◽

Refractory Anemia ◽

Sideroblastic Anemia ◽

Ring Sideroblasts ◽

Amino Acid Mutations

Abstract Abstract 4225 Introduction: Sideroblastic anemia is characterized by anemia with the emergence of ring sideroblasts in the bone marrow. There are two forms of sideroblastic anemia. One is an inherited sideroblastic anemia, and another is an acquired sideroblastic anemia. Because sideroblastic anemia is a rare disease, there are few comprehensive studies of sideroblastic anemia, including clinical and genetic information. In the present study, we have performed national-wide survey of sideroblastic anemia in Japan to investigate the epidemiology and pathogenesis of the disease. Method: This study consists of three-step surveys. First, the patients of sideroblastic anemia were searched by simple questionnaire to hematological department of hospitals in all areas in Japan (first investigation). Next, detailed clinical information of sideroblastic anemia patients were collected (second investigation). Survey items were age of onset, gender, family history, hematology, bone marrow and biochemical findings. Then, genetic analyses of patients who were suspected inherited sideroblastic anemia were performed (third investigation). For the genetic analysis, mutations of ALAS2, ABC7, GLRX5, SLC25A38, which are known to be responsible genes for inherited sideroblastic anemia, were examined. Result: At the first investigation, sideroblastic anemia patients were surveyed in the 1086 institutions of Japan. There were 14 cases of confirmed or suspected cases of inherited sideroblastic anemia and 285 cases of suspected or confirmed cases of acquired sideroblastic anemia. These patients were subjects of second investigation. As of August 9, data of 99 patients have been collected. In these cases there are 7 cases of confirmed inherited sideroblastic anemia, 7 cases of suspected inherited sideroblastic anemia, 28 cases of refractory anemia with ring sideroblasts (MDS-RARS) and 57 cases of refractory cytopenia with multilineage dysplasia with ring sideroblasts (MDS-RCMD-RS). Median age of onset was 70.5 years old in MDS-RCMD-RS cases, whereas that of cases in inherited sideroblastic anemia was 14 years old. Hemoglobin level in inherited sideroblastic anemia and RCMD-RS was 6.7g/dl and 8.3g/dl. MCV was 64.7 fl, 105.1 fl in inherited sideroblastic anemia and RCMD-RS. There was thus significant different between MCV level in inherited sideroblastic anemia and RCMD-RS. Chromosomal abnormality of +8 and idic (X) (q13), associated with ABC7 gene, were detected in 7 and 2 of 25 RCMD-RS patients, respectively. At the moment, 4 confirmed and 4 suspected patients of inherited sideroblastic anemia proceeded to third investigation. As a result, mutations of ALAS2, which is the first enzyme of heme biosynthesis in erythroid cells, have been identified in 6 out of 8 patients. The amino acid mutations were detected in exon 5 (R170C, R170L), exon 9 (R411C, R452C), and exon 11 (V562A). For patients without mutations in ALAS2 gene, mutations of other genes related to inherited sideroblastic anemia have been analyzed; however, no mutations are identified so far. Conclusion: The results showed that RCMD-RS is most common in sideroblastic anemia, and XLSA is most frequent type of inherited sideroblastic anemia. However, there are significant number of suspected cases of inherited sideroblastic anemia. The genetic analysis of these cases, including RARS without chromosomal anomaly, is currently in progress. This research has been supported by Grant-in-Aid for Scientific Research from Ministry of Health, Labour and Welfare of Japan. Disclosures: No relevant conflicts of interest to declare.

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