scholarly journals A case of Roberts syndrome: its ultrasonographic characteristics and genetic diagnosis

2020 ◽  
Vol 28 (3) ◽  
pp. 212-216
Author(s):  
Reyhan Ayaz ◽  
Emine Göktaş ◽  
Mine Balasar
Keyword(s):  
Skeletal Dysplasia ◽  
Genetic Disease ◽  
Genetic Diagnosis ◽  
Autosomal Recessive Inheritance ◽  
Cardiac Anomaly ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Molecular Analyses ◽  
Roberts Syndrome ◽  
Genetic Consultation

Objective: Roberts syndrome is a very rare genetic disease, and it has an autosomal recessive inheritance pattern. It develops as a result of the mutation in ESCO2 gene located in the 8th chromosome. In our study, we aimed to present a case which was found to have Roberts syndrome coexisting with multiple anomalies, particularly skeletal system anomaly, in the 17 weeks of gestation. Case(s): In the fetal ultrasonographic evaluation performed on the pregnant women who referred to our hospital for routine gestational examination in the 17 weeks of gestation, anomalies in the bilateral upper and lower extremities, contracted legs, bilateral cleft palate and lip, intrauterine growth restriction and cardiac anomaly were found in the fetus. Roberts syndrome was considered first with these ultrasonographic findings. The diagnosis of Roberts syndrome was confirmed by cytogenetic and molecular analyses. Early segregation of centromeres and early breaking up of heterochromatic regions near centromeres were found at metaphase stage. By cytogenetic and molecular analyses, homozygous mutation in ESCO2 gene of the fetus and heterozygous mutation in the parents were found. The termination of pregnancy was decided after the genetic consultation with the parents. Physical examination findings and prenatal ultrasound findings after termination were found similar. Conclusion: Many severe skeletal dysplasia cases can be diagnosed ultrasonographically before 20 weeks of gestation. Early diagnosis ensures to take necessary actions for medical support during postnatal period and in terms of labor if pregnancy continues as well as genetic consultation opportunity. If the genetic disease that causes skeletal dysplasia can be identified and parents are found to have this gene, healthy pregnancies can be achieved by obtaining normal embryos via pre-implantation genetic diagnosis in order to prevent the relapse of the disease.

scholarly journals The Molecular Diagnosis of Patients with Vein Thrombosis Due to Deficiency of Inherited Anticoagulant Proteins

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1535-1535
Author(s):  
Rong-Fu Zhou ◽  
Bo Gao ◽  
Jian Ou-Yang
Keyword(s):  
Missense Mutation ◽  
Promoter Region ◽  
Protein C ◽  
Conflicts Of Interest ◽  
Genetic Diagnosis ◽  
Protein S ◽  
Deletion Mutation ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Thrombin Time

Abstract Objective: To make genetic diagnosis and pedigree analysis for patients with recurrent venous thromboembolism due to inherited deficiency of protein C (PC), protein S (PS). Methods: The routine coagulation tests including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) were performed. Chromogenic substrate assay was used to detect the activities of Protein C (PC:C), total Protein S (PS:C) and antithrombin (AT:C). All exons and their flanks of PC and PS gene were amplified by polymerase chain reaction (PCR). The PCR products were sequenced directly and blastered to normal sequence of corresponding anti-coagulant protein to find the gene mutations. Results: Totally nine probands with DVT or PE were enrolled, their peripheral blood and medical histories collected after informed consents. Proband 1, 2 and 3 were with combined deficiency of PC and PS, while proband 4 was with PC deficiency. Sequencing of PC gene showed there were polymorphism sites G4880A, C4867T and A5054T in promoter region for all four probands with PC deficiency. PC:C and PS:C for proband 1 was 48% and 26.3%, respectively. PC gene sequencing showed that there was a heterozygous mutation A6578T in exon2 region, resulting in Thr18Ser. Sequencing of PS gene showed there was G68395T heterozygous mutation in exon4 region, leading to Arg90Leu. PC:C and PS:C of proband 2 was 27% and 22.9%, respectively. Heterozygous mutations of G68428A and C68430T in exon4 region of PS gene were found, leading to Arg100His and Gln101Stop, respectively. Proband 3 was with PC deficiency and PS deficiency, PC:C and PS:C were 58% and 57.3%. Heterozygous AGA12702-12704 or AGA12705-12707 deletion mutation was found in Exon2 of PC gene resulting in Arg192del or Arg193del, and heterozygous missense mutation A15240G in Exon9 resulting in His370Arg. Heterozygous mutation G68395T and G825512C was found in Exon4 and Exon9 region of PS gene, respectively, resulting in Arg90Leu and Ser321Thr. Proband 4 was with PC deficiency, PC:C50%. There was no other mutation detected except for polymorphism sites in promoter region. Proband 5 was with PS deficiency, PS:C 38.8%. Heterozygous mutation G68395T in exon4 region was detected, leading to Arg90Leu. Homozygous mutation C102102T was found in Exon14 region,leading to Gla616Val. Proband 6 was with PS deficiency, PS:C 35.2%. Heterozygous mutations G68395T andC68430T in Exon4 were found, leading to Arg90Leu and Gln101Stop, respectively. Proband 7 was with PS deficiency, PS:C 43.7%.Homozygous mutation C102102T in exon14 region was detected, resulting in Gla616Val. Proband 8 was with PS deficiency, PS:C43.6%. Heterozygous mutation G68395T and C68430T in exon4 region was found, leading to Arg90Leu and Gln101Stop. Proband 9 was with PS deficiency, PS:C 7.7%. Two of his family members were also with PS deficiency (II2，III2） with heterozygous mutation G68395T in Exon4 region（II1，II2，III1，III2）, leading to Arg90Leu. Conclusions: Polymorphisms of G4880A, C4867T and A5054T in promoter region, missense mutation A6578T, A15240G, AGA12702-12704 or 12705-12707 deletion mutation in PC gene，missense mutation G68395T, G68428A, C86066T, G82512C, C102102T, and nonsense mutation C68430T in PS gene might be the cause of reduced activities of corresponding anticoagulant proteins. All these mutations, except for C86066T in PS gene, which had been reported in Hongkong, are de novo ones. Disclosures No relevant conflicts of interest to declare.

Two siblings with metachromatic leukodystrophy caused by a novel identified homozygous mutation in the ARSA gene

2018 ◽  
Vol 31 (9) ◽  
pp. 1047-1051 ◽  
Author(s):  
Mahmut Aslan ◽  
Serkan Kirik ◽  
Bilge Özgör ◽  
Serdal Güngör
Keyword(s):  
Genetic Analysis ◽  
Metachromatic Leukodystrophy ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Inherited Disease ◽  
Normal Ranges ◽  
Clinical Presentations ◽  
The One

Abstract Background Metachromatic leukodystrophy (MLD) is an autosomal recessively (AR) inherited disease caused by the deficiency of the enzyme arylsulfatase A (ARSA). Although MLD is the most common form of hereditary leukoencephalopathy, it is still very rare. More than 200 gene mutations have been identified in the ARSA gene. The most frequently identified mutation is the one located on chromosome 22q13.33. In the present study, new mutations are reported in two siblings of different ages and with different clinical presentations. Case presentation A 9-year-old male patient, suffering from ataxia, attention deficit and perceptual difficulties, was first seen at the age of 7. While the findings of neurological examination and neuroradiological evaluation suggested MLD, the ARSA enzyme levels were analyzed and found to be at a lower limit. Genetic analysis revealed variant homozygous mutations of the ARSA gene at p.N352S/c.1055T>C in exon 6 and at p.E331K/c.991G>A in exon 7. In the genetic analysis of his three siblings and parents, a variant heterozygous mutation of the ARSA gene was detected at p.N352S/c.1055T>C in exon 6 and at p.E331K/c.991G>A in exon 7. Conclusions MLD is a rare disease; however, it is likely to find different variant forms in our population, in which the frequency of consanguineous marriages is high. Genetic diagnosis is important in symptomatic cases with enzyme levels within the normal ranges.

scholarly journals the Prevalence of UGT1A1*93 and ABCC5 Polymorphisms in Cancer Patients Receiving Irinotecan-Based Chemotherapy at Al-Najaf Al-Ashraf

2019 ◽  
Vol 28 (2) ◽  
pp. 24-29
Author(s):  
Ahmed F. Al_talkani ◽  
Sarmed H. Kathem
Keyword(s):  
Cancer Patients ◽  
Topoisomerase I ◽  
Antineoplastic Agent ◽  
Limiting Factors ◽  
Cancer Center ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Wild Type ◽  
Isolation And Purification ◽  
Wide Range

Irinotecan (CPT-11) is a semisynthetic derivative of the antineoplastic agent camptothecin used in a wide range as an anti-cancer agent in many solid tumors because of its cytotoxic effect through the interaction with the topoisomerase I enzyme. The major limiting factors for irinotecan treatment are its association with potentially life-threatening toxicities including neutropenia and acute or delayed-type diarrhea, results from distinct interindividual and interethnic variability due to gene polymorphism. This is a cross sectional pharmacogentics study was conducted on 25 cancer patients to estimate the prevalence of UGT1A1*93 and ABCC5 allele single nucleotide polymorphism (SNP) in Iraqi cancer patients treated with irinotecan-based therapy at Middle Euphrates Cancer Center. Four drops of venous blood was drawn for each patient and was applied onto the FTA classic card to perform a genotyping assay for the 2 SNPs. After DNA isolation and purification, real time PCR was performed to detect the SNPs of each gene. Results of this study showed the prevalence of one allele variant (heterozygous mutation) of UGT1A1*93 was 64% compared to 36% of patients were wild type to this SNP. No patient (0%) could be detected with homozygous polymorphism of the UGT1A1*93. For the ABCC5 polymorphism, results revealed that 32% of patients have one polymorphic allele (heterozygous), while 28% of them have two polymorphic alleles (homozygous mutation). Wild type ABCC5 gene constitutes 40% of patients.   As a conclusion, high prevalence of UGT1A1*93 and ABCC5 polymorphic alleles were detected in patients at Middle Euphrates Cancer Center which may explain the high toxicity features associated with irinotecan therapy. 

Abstract 9600: Abnormal Lipoprotein Metabolism Other Than LDL Fraction in Familial Hypercholesterolemia: Serial analysis using Ultracentrifugation Method

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Hayato Tada ◽  
Masa-aki Kawashiri ◽  
Akihiko Hodatsu ◽  
Chiaki Nakanishi ◽  
Tetsuo Konno ◽  
...  
Keyword(s):  
Risk Factor ◽  
Familial Hypercholesterolemia ◽  
Plasma Levels ◽  
Lipoprotein Metabolism ◽  
Clinical Impact ◽  
Lipoprotein Fraction ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Additive Risk ◽  
Few Data

Background: It is well known that familial hypercholesterolemia (FH) is a common inherited disorder that could cause marked elevation of plasma LDL-C level. However, few data exists regarding the clinical impact of plasma levels of VLDL-C and IDL-C as well as the composition of each lipoprotein fraction in FH. Thus, we assessed the hypothesis that the abnormality in LDLR modulates the quality as well as the quantity of lipoprotein other than LDL fraction. Methods: We investigated the plasma lipoprotein by ultracentrifugation method about 146 controls (mean age=61.4±17.1yr, mean LDL-C=92.7±61.2mg/dl), 213 heterozygous mutation-determined FH subjects (mean age=46.0±18.0yr, mean LDL-C=225.1±61.2mg/dl), and 16 homozygous mutation-determined FH subjects (mean age=26.9±17.1yr, mean LDL-C=428.6±86.1mg/dl). In addition, we evaluated the composition of each lipoprotein fraction by calculated cholesterol ester (CE) / triglyceride (TG) ratio. Results: As shown in the figure, the differences of the levels of TC and LDL-C between these 3 groups as well as those of VLDL-C (19.5±10.4, 25.2±19.3, 29.5±21.4 mg/dl, respectively) and IDL-C (8.3±3.7, 16.8±11.5, 40.0±37.3 mg/dl, respectively) were statistically significant. Moreover, the ratios of CE/TG of each lipoprotein fraction significantly increased in heterozygous FH and homozygous FH group, compared with that of controls, suggesting that the abnormality in LDLR modulate the quality as well as the quantity of each lipoprotein fraction. Conclusions: Our results indicate that LDLR participate not only in metabolism of LDL fraction but also in that of VLDL and IDL fractions. Larger amounts of VLDL-C and IDL-C with worse quality should also be additive risk factor in FH subjects.

scholarly journals BETA-GLOBIN GENE MUTATIONS IN TURKISH CHILDREN WITH BETA-THALASSEMIA: RESULTS FROM A SINGLE CENTER STUDY

2013 ◽  
Vol 5 (1) ◽  
pp. e2013055 ◽  
Author(s):  
Ali Fettah ◽  
Cengiz Bayram ◽  
Nese Yarali ◽  
Pamir Isik ◽  
Abdurrahman Kara ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Thalassemia Intermedia ◽  
Turkish Children ◽  
Tertiary Center

Introduction: The beta thalassemias are common genetic disorders in Turkey and in this retrospective study our aim was to evaluate β-globin chain mutations and the phenotypic severity of β-thalassemia patients followed-up in our hospital, a tertiary center which serves patients from all regions of Turkey. Materials and Methods: 106 pediatric patients were analysed for β-globin gene mutations by using DNA analysis. Patients were classified as having β-thalassemia major or β-thalassemia intermedia based on age at diagnosis, transfusion frequency and lowest hemoglobin concentration in between transfusions. Results: There were 106 patients (52.8% female and 47.2% male) with a mean age of 11.2±5 years (1.6 – 22.3 years). Eighty-four (79.2%) patients had β-thalassemia major, whereas the remaining 22 patients (20.8%) were identified as having β-thalassemia intermedia. Overall, 18 different mutations were detected on 212 alleles. The most frequently encountered mutation was IVS I.110 (G>A) (35.3%), followed by Codon 8 del-AA (10.4%), IVS II.1 (G>A) (8%), IVS I.1 (G>A) (7.5%), Codon 39 (C>T) (7.1%) and Codon 5 (-CT) (6.6%), which made up 79.4% of observed mutations. According to present results, IVS I.110 (G>AA) was the most frequent mutation observed in this study, as in other results from Turkey. Evaluation of β-thalassemia mutations in 106 patients with 212 alleles, revealed the presence of homozygous mutation in 85 patients (80.2%) and compound heterozygous mutation in 21 patients (19.8%). The mutations detected in patients with homozygous mutation were IVS I.110 (G>A) (38.8%), Codon 8 del –AA (11.8%), IVS II.1 (G>A) (8.2%) and IVS I.1 (G>A) (8.2%). Observed mutations in the compound heterozygotes were Codon 39 (C>T)/Codon 41-42 (-CTTT) (14.3%), IVS I.110 (G>A)/Codon 39(C>T) (14.3%), IVS I.110 (G>A)/Codon 44(-C) (14.3%), and IVS II.745 (C>G)/ 5’UTR + 22 (G>A) (9.5%). Conclusion: Our hospital is a tertiary referral center that provides care to patients from all over the country, and thus the distribution of mutations observed in the current study is significant in term of representing that of the country as a whole.

Novel Homozygous Mutation (R329X) in the Hemojuvelin Gene Is Associated with Hypogonadotrophic Hypogonadism, Diabetes Mellitus and Heart Failure Duo to Juvenile Hemochromatosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5102-5102
Author(s):  
Rong-Fu Zhou ◽  
Jian Ouyang ◽  
Xue-mei Guo ◽  
Bing Chen ◽  
Jing-yan Xu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Nonsense Mutation ◽  
Conflicts Of Interest ◽  
Heterozygous Mutation ◽  
Iron Level ◽  
Homozygous Mutation ◽  
Ferritin Concentration ◽  
Hypogonadotrophic Hypogonadism ◽  
Juvenile Hemochromatosis

Abstract Abstract 5102 Juvenile hemochromatosis (JH) is a rare autosomal recessive disorder characterized by the early onset of severe iron overload. A large variety of mutations within the genes encoding hepcidin (HAMP) and hemojuvelin (HJV) have been identified in patients with JH. But in the Chinese population, the prevalence of JH is quite low. No HJV mutation has been reported so far. Methods and results The proband was a 25-year-old young man of Asia decent presented with hypogonadotrophic hypogonadism, diabetes mellitus and heart failure but no family history of iron disorders. His serum iron level was 34μmol/L, with a transferrin concentration of 8.5g/L, serum ferritin concentration was 8140 μg/L. Echocardiography revealed that he had generalized cardiac enlargement, cardiac dysfunction, and severe mitral and tricuspidal insufficiency, pulmonary hypertension. Ultra-sonography showed diffuse hepatomegaly and splenomegaly, seroperitoneum and right hydrothorax. Liver biopsy showed severe diffuse hepatocellular siderosis and cirrhosis,hemosiderin pigmentation. To search for possible variants in the HJV gene, we performed PCR and direct sequencing in proband and his family. A homozygous nonsense mutation in exon 4 of HJV (R329X) was identified in the JH patient and heterozygous mutation of R329X in his father and mother. No mutations were found in other genes associated with adult or juvenile hemochromatosis including HFE, transferrin receptor-2 (TFR2), ferroportin (SLC40A1), hepcidin (HAMP). Conclusions A novel nonsense mutation (R329X) has been identified in the HJV gene for the first time in China. This mutation elevates ferritin levels and leads to JH associated with hypogonadotrophic hypogonadism, diabetes mellitus and severe cardiomyopathy. Disclosures No relevant conflicts of interest to declare.

Analysis of the JAK2 Gene cDNA Full-Length In One Chinese Familial Myeloproliferative Disorders

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5056-5056
Author(s):  
Ru Feng ◽  
Lixia Hao ◽  
Yongmin Zhang ◽  
Yongqiang Wei ◽  
Fen Huang ◽  
...  
Keyword(s):  
Family Members ◽  
Gene Mutations ◽  
Myeloproliferative Disorders ◽  
Full Length ◽  
The Other ◽  
Jak2v617f Mutation ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
The Family

Abstract Abstract 5056 Introduction: JAK2V617F point mutation have been confirmed to be one of the major molecular mechanism of BCR/ABL negative myeloproliferative disorders(MPD). Besides, some other gene mutations such as JAK2 exon12, MPL W515L/K, c-mpl and EPOR have extended the scope of the research in this field. Most of the MPD patients are sporadic and there are seldom reports in Chinese familial MPD. 2008 ASH metting we have reported in a Chinese family of MPD's findings, the two brothers in our hospital diagnosis for MPD (one is a PV, another is ET), then we investigated the 15 members of the family. We discovered that there were three male members carried the JAK2V617F mutation in this family, including the two MPD patients and their father, which affected in two generations. All the family members were confirmed as BCR/ABL, MPL W515L/K, c-mpl, and EPOR negative. Subsequently, in order to understand the existence of family members in addition to the gene JAK2 V617F mutation, the existence of JAK2 gene mutations in other parts of the? if other mutations in existence and the high incidence of family members of MPD? We focus on the cDNA full-length of JAK2 gene to provide some theory basis on the pathogenesis in MPD. Methods: A total of 15 family members were enrolled in our study, including 2 brothers of MPD patients (the older one was thrombocythemia (ET), and another is polycythemia vera (PV)) and the other members in the same family. The mRNA of mononuclear cells from peripheral blood sample was extracted according to the manufacturer's instruction (TAKARA). RT-PCR and DNA sequencing have been used to analyze the cDNA full-length of the JAK2 gene. Results: All of the samples can be analyzed for JAK2 cDNA full-length. 3 members carried the JAK2V617F mutation (1849G®T) in this family, including the two MPD patients and their father. And the older brother was homozygous mutation and the other two were heterozygous mutation. All of the 15 samples were JAK2 exon12 gene mutation negative. 2 persons who were the male ET patient's children had a heterozygous mutation (380G®A) in JAK2 exon 3, caused a glycine-to-asparticacid substitution at position 127. Besides, 13 persons had 489C®T mutation in exon 4 and 14 persons had 2490G→A mutation in exon 17 in this family, But they were both same-sense mutation. Conclusion: It is necessary to do routine analysis of blood and other related inspection for MPD patient's family members, so as to make diagnosis earlier. However, we are not sure that the sequencing results are unique to all the familial MPD and need to be confirmed by more cases. We still do not determine the current discovery point mutations have biological significance, still need to be further explored. Disclosures: No relevant conflicts of interest to declare.

Absence of Band 3 in Severe Dyserythropoietic/Hemolytic Anemia with Complete Distal Renal Acidosis and a Novel Homozygous Exon 12 C.1430C>a (p.Ser477X) SLC4A1 Gene Mutation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 945-945 ◽  
Author(s):  
Leo Kager ◽  
Lesley J Bruce ◽  
Joanna F Flatt ◽  
Petra Zeitlhofer ◽  
Gerhard Fritsch ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Conflicts Of Interest ◽  
Stop Codon ◽  
Disease Process ◽  
Failure To Thrive ◽  
Autosomal Recessive Inheritance ◽  
Band 3 ◽  
Southeast Asian ◽  
Heterozygous Mutation ◽  
Exon 11

Abstract The solute carrier 4A1 gene (SLC4A1) encodes theband 3 or bicarbonate anionic exchanger 1 (AE1). It is not only the major glycoprotein of the red blood cell (RBC) membrane but also expressed in acid secreting alpha-intercalated kidney cells. Functionally impairing SLC4A1 mutations reduce the expression and/or activity of AE1 thereby causing a unique combination of hemolytic anemia and distal renal tubular acidosis (dRTA). So far, only four such particular homozygote mutations have been documented in humans: an exon 11 p.400-408 deletion in Southeast Asian ovalocytosis (SAO) with transfusion-dependent dyserythropoietic anemia and dRTA (Picard et al, Blood 123:1963;2014), an exon 13 p.V488M mutation in transfusion-dependent hereditary spherocytosis (HS) and dRTA lacking band 3 (Ribeiro et al, Blood 96:1602;2000), an exon 16 p.S667F mutation in transfusion-dependent HS and incomplete dRTA (Toye et al, Blood 111:5380;2008), and finally an exon 19 p.Ala858Asp in a compensated hemolytic anemia with marked acanthocytosis, echinocytosis and dRTA (Fawaz et al, Europ J Haematol 88:350;2012). We report herein a novel homozygote variant in exon 12 in a patient with a transfusion-dependent dyserythropoietic/hemolytic anemia and complete dRTA. The now 4-years old Turkish boy was born after 32 weeks of gestation and presented with a severe hemolytic anemia (Hb 40 g/L) that required exchange transfusions and a complete dRTA that was treated with oral bicarbonate. He also suffered from delayed psychomotoric developmental with failure to thrive, trigonocephalus and strabismus convergens. Bone marrow smears showed marked dyserythropoiesis but normal myeloid and megakaryocytic lineages. Although necessary monthly transfusions impeded the patient's direct diagnostic work-up, a flow cytometric eosin-5-maleimide assay eventually revealed a reduced staining of his consanguine parents' and his two siblings' erythrocytes, who all had subclinical signs of spherocytosis despite normal RBC counts. Based on these findings, we analyzed the SLC4A1 gene and found two homozygous sequence variants in the patient, namely a novel disease-relevant exon 12 nonsense mutation c.1430C>A (p.Ser477X) and a disease-unrelated c.2312-48T>G (rs13306780). The ensuing stop codon of the former truncates the protein, prevents band 3 formation and reduces glycophorin A expression. Bright field imaging uncovered few phenotypic spherocytic band 3 null RBCs even in the peripheral blood. In accordance with the autosomal recessive inheritance pattern, both healthy parents as well as his healthy siblings were found to be heterozygous carriers. The band 3 protein was reduced to 50-60% in the parents' erythrocytes. An increased approximately 22 kDa-sized band was evident in Coomassie stained gels of the heterozygous mutation carriers' membrane preparations and classified by immunoblotting as peroxiredoxin 2 (PRDX2), which plays a major role in protecting RBCs from oxidative stress. Taken together, the provided data clearly confirm the relevance of this particular c.1430C>A (p.Ser477X) SLC4A1 mutation in the disease process. Of note, such a severe dyserythropoietic anemia and complete dRTA was also recently reported in a patient with Southeast Asian ovalocytosis and another form of homozygous SLC4A1 mutation (Picard et al, Blood 123:1963;2014). Disclosures No relevant conflicts of interest to declare.

New and Inherited STAT1 Mutations in a Chinese Family with Chronic Mucocutaneous Candidiasis: A Case Report

2020 ◽  
Author(s):  
Xiaoheng XU ◽  
Wenxia MENG ◽  
Lu FENG ◽  
Wei GUO
Keyword(s):  
Human Gene ◽  
Genetic Diagnosis ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Chronic Mucocutaneous Candidiasis ◽  
Dna Binding Domain ◽  
Oral Medicine ◽  
Mucocutaneous Candidiasis ◽  
Mutation Database ◽  
First Time

A mild clinical Chronic Mucocutaneous Candidiasis (CMC) phenotype with STAT1 transcription factor mutation has been identified in a Chinese family. It is a rare variant in STAT1 (NM_0073315.3c.1175T>C Met392Thr). Specifically, it is a heterozygous mutation. To date, the pathogenicity of this variant in STAT1 (NM_0073315.3c.1175T>C Met392Thr) for CMC has not been reported in the Human Gene Mutation Database. Thus, this is the first report about STAT1 mutation found in CMC patients from Chinese ethnic group. This study also shows the mutation on the DNA-binding domain of STAT1 for the first time. The findings will broaden the spectrum of STAT1 mutations and facilitate genetic diagnosis by the oral medicine specialists.

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