scholarly journals Clinical and genetic diagnosis of thirteen Japanese patients with hereditary spherocytosis

2022 ◽  
Vol 9 (1) ◽  
Author(s):  
Keiko Shimojima Yamamoto ◽  
Taiju Utshigisawa ◽  
Hiromi Ogura ◽  
Takako Aoki ◽  
Takahiro Kawakami ◽  
...  

AbstractHereditary spherocytosis is the most frequent cause of hereditary hemolytic anemia and is classified into five subtypes (SPH1-5) according to OMIM. Because the clinical and laboratory features of patients with SPH1-5 are variable, it is difficult to classify these patients into the five subtypes based only on these features. We performed target capture sequencing in 51 patients with hemolytic anemia associated with/without morphological abnormalities in red blood cells. Thirteen variants were identified in five hereditary spherocytosis-related genes (six in ANK1 [SPH1]; four in SPTB [SPH2]; and one in each of SPTA1 [SPH3], SLC4A1 [SPH4], and EPB42 [SPH5]). Among these variants, seven were novel. The distribution pattern of the variants was different from that reported previously in Japan but similar to those reported in other Asian countries. Comprehensive genomic analysis would be useful and recommended, especially for patients without a detailed family history and those receiving frequent blood transfusions due to chronic hemolytic anemia.

2020 ◽  
Author(s):  
Yating Tang ◽  
Jie Xu ◽  
Tianyu Zheng ◽  
Yi Lu

Abstract Background: To identify the underlying genetic defect responsible for microphthalmos eyes in two three-generation Chinese families.Methods: In our study, we screened 425 potential eye disease-related genes of the proband of a three-generation Chinese family diagnosed with microphthalmos using next-generation sequencing-based target capture sequencing. Variants were filtered and analyzed to identify possible disease-causing variants before Sanger sequencing validation.Results: We enrolled two families with microphthalmos (Family 1: microphthalmos with congenital ocular coloboma and Family 2: simple microphthalmos). Two novel heterozygous mutations, PXDN c.3165C>T (p.Pro1055Pro) and PXDN c.2640C>G (p.Arg880Arg), were found in Family 1, and CRYBB2 c.481G>A (p.Gly161Arg) was found in Family 2, but none of the mutations were found in the unaffected individuals, who were phenotypically normal. Multiple orthologous sequence alignment (MSA) revealed that the CRYBB2 p.Gly161Arg mutation was a deleterious effect mutation.Conclusions: The three novel mutations found in our study extend our current understanding of the genetic basis of microphthalmos and provide early presymptomatic diagnosis and emphasize the significance of genetic diagnosis of microphthalmos.


Blood ◽  
1956 ◽  
Vol 11 (4) ◽  
pp. 324-337 ◽  
Author(s):  
R. K. SMILEY ◽  
H. DEMPSEY ◽  
P. VILLENEUVE ◽  
J. S. CAMPBELL ◽  
BARBARA BEST

Abstract 1. The genetic, clinical and hematologic features of an atypical chronic hemolytic anemia in two siblings of a French Canadian family have been described. 2. The anemia is normocytic, normochromic and not associated with any characteristic morphologic abnormality of the red cells. 3. Slight increases in osmotic and incubated mechanical fragility, as well as a more definite increase in aumtohemolysis were found which could not be demonstrated after splenectomy. 4. The survival time of normal red cells was shortened before splenectomy in one patient. Normal red cell survival was demonstrated in both patients after splenectomy. 5. The features which differentiate this hemolytic anemia from hereditary spherocytosis are discussed. 6. French or French Canadian ancestry has been noted in some of the reported patients most similar to our own. 7. The association of this type of hemolytic anemia with blood group A has been confirmed in our patients. 8. Splenectomy decreased the severity of the hemolytic process in both patients. This benefit may have resulted from removal of an extracorpuscuar hemolytic mechanism.


Blood ◽  
1970 ◽  
Vol 36 (3) ◽  
pp. 310-320 ◽  
Author(s):  
PHILLIP STURGEON

Abstract The purpose of this report is to direct attention of hematologists to a mild chronic hemolytic anemia, of unexplained etiology, characterized by the remarkable absence of all Rh-Hr factors. There are also defects in the Ss, U blood group determinants. The anemia has most of the routine hematological characteristics of mild stomatocytosis and/or hereditary spherocytosis. Like hereditary spherocytosis, it shows no abnormalities of intraerythrocytic enzymes nor of membrane lipids. Unlike hereditary spherocytosis, however, its inheritance is recessive. The proposed basis for this hemolytic anemia is homozygosity for a gene whose normal allele produces components of the erythrocyte membrane which function in the maintenance of intracellular osmotic equilibrium and which serves as substrate for the action of both the products of the Rh-Hr genes and of the genes of the MNSs, U and, possibly, of the Fy systems.


2020 ◽  
Vol 33 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Tatsushi Tanaka ◽  
Kohei Aoyama ◽  
Atsushi Suzuki ◽  
Shinji Saitoh ◽  
Haruo Mizuno

AbstractObjectivesCongenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations.MethodsWe enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH.ResultsWe identified potentially pathogenic bi-allelic variants in DUOX2, TSHR, and TPO in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in NKX2-1 (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (DUOX2, TSHR, TG, DUOXA2, and TPO) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic DUOX2 variants showed a more severe clinical presentation in infancy than those with bi-allelic TSHR variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic DUOX2 variants.ConclusionsThe prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.


PEDIATRICS ◽  
1986 ◽  
Vol 78 (1) ◽  
pp. 183-184
Author(s):  
J. J. LEFRÈRE ◽  
A. M. COUROUCÉ ◽  
J. P. SOULIER ◽  
M. P. CORDIER ◽  
M. C. GUESNE GIRAULT ◽  
...  

To the Editor.— Human parvovirus is already known to be responsible for aplastic crisis in chronic hemolytic anemia,1 for erythema infectiosum or fifth disease,2 and for arthropathies,3,4 and it has recently been isolated from the serum of patients with vascular purpura.5 We report the case of Henoch-Schonlein purpura associated with human parvovirus infection. H. T., a 6-year-old girl, without any significant past history, was admitted on March 8, 1985, for joint pain and swelling (wrists, knees, ankles) associated with intense abdominal pain.


2021 ◽  
Author(s):  
Yujiro Higuchi ◽  
Masahiro Ando ◽  
Akiko Yoshimura ◽  
Satoshi Hakotani ◽  
Yuki Koba ◽  
...  

AbstractThe presence of fragile X mental retardation 1 (FMR1) premutation has been linked to patients with a certain type of cerebellar ataxia, the fragile X-associated tremor/ataxia syndrome (FXTAS). However, its prevalence in Japan has yet to be clarified. The aim of the present study is to determine the prevalence of FXTAS in Japanese patients with cerebellar ataxia and to describe their clinical characteristics. DNA samples were collected from 1328 Japanese patients with cerebellar ataxia, referred for genetic diagnosis. Among them, 995 patients with negative results for the most common spinocerebellar ataxia subtypes were screened for FMR1 premutation. Comprehensive clinical and radiological analyses were performed for the patients harbouring FMR1 premutation. We herein identified FMR1 premutation from one female and two male patients, who satisfied both clinical and radiological criteria of FXTAS (0.3%; 3/995) as well. Both male patients presented with high signal intensity of corticomedullary junction on diffusion-weighted magnetic resonance imaging, a finding comparable to that of neuronal intranuclear inclusion disease. The female patient mimicked multiple system atrophy in the early stages of her disease and developed aseptic meningitis with a suspected immune-mediated mechanism after the onset of FXTAS, which made her unique. Despite the lower prevalence rate in Japan than the previous reports in other countries, the present study emphasises the necessity to consider FXTAS with undiagnosed ataxia, regardless of men or women, particularly for those cases presenting with similar clinical and radiological findings with multiple system atrophy or neuronal intranuclear inclusion disease.


Blood ◽  
1968 ◽  
Vol 32 (1) ◽  
pp. 33-48 ◽  
Author(s):  
WOLF W. ZUELZER ◽  
ABNER R. ROBINSON ◽  
THERESA H. J. HSU

Abstract Extreme intrafamilial differences between PK-deficient phenotypes regarding hemolysis, ATP stability, and glucose consumption were observed in two pedigrees in which the index cases had severe nonspherocytic hemolytic anemia. Genetic analysis was consistent with heterozygosity for two distinct interacting mutants in minimally affected relatives of severely anemic homozygotes. Neither the mature erythrocytes of the former nor the reticulocyte-rich cell populations of the latter showed accumulation of glycolytic intermediates, but 2,3-DPG was elevated in both. Despite severe PK deficiency, red cell survival in the minimal type was near normal, glucose consumption was unaffected in three of four subjects tested, and ATP maintenance in vitro was adequate, in contrast to the severe type in which these parameters were grossly depressed. The genetic and pathophysiologic implications of these findings are discussed. The possibility is considered that defective glycolysis may play a subordinate role in the hemolytic process associated with PK deficiency and that the enzyme defect may be a genetic marker for as yet unknown erythrocytic abnormalities involving an increase of 2,3-DPG and possibly primary membrane lesions creating excessive demands on the energy metabolism of the erythrocytes. Regardless of the mode of gene action, it is concluded that the nonspherocytic hemolytic anemias associated with PK deficiency are genetically and phenotypically heterogeneous, and that the genetic diagnosis cannot rest on PK assay alone.


2021 ◽  
Vol 30 (2) ◽  
pp. 51-58
Author(s):  
Amal M. Matta ◽  
Elsayed M. Abd-Elghany ◽  
Abeer A. Aboelazm ◽  
Osama Abo. Zaki, ◽  
Doaa Abd. Shaker

Background: Due to the tropism of human parvovirus B19 to erythroid progenitor cells, infection in patients with an underlying hemolytic disorder such as thalassemia, hereditary spherocytosis, sickle cell disease and Glucose-6-phosphate dehydrogenase deficiency leads to suppression of erythrocyte formation, referred to as transient aplasia crisis (TAC), which may be life-threatening. Objectives: Detection of parvovirus B19 DNA and its IgG antibodies in the serum of children with chronic hemolytic anemia and in apparently healthy children in Benha University Hospitals. Methodology: The study was conducted on 80 children. Forty of them with chronic hemolytic anemia, they were subdivided into 2 groups, Group (1a) included 20 patients without history of aplastic crisis, Group (Ib) included 20 patients with a history of aplastic crisis and 40 age and sex-matched apparently healthy children representing control (Group II). All patients were subjected to full history taking, clinical examination and laboratory investigations. Parvovirus B19 IgG was measured using anti-parvovirus B19 ELISA kits (SUNRED), and parvovirus B19 DNA was detected by using nestedpolymerase chain reaction. Results: The seroprevalence of parvovirus B19 IgG was significantly higher (P value =0.016) in Group Ia (50%) (10 out of 20) and Group Ib (45%) (9 out of 20) than the control group (Group II) (17.5%) (7 out of 40). There was a significant positive correlation between anti-parvovirus B19 IgG and age of all patients, frequency of blood transfusion. The prevalence of parvovirus B19 DNA was 10% (2 out of 20) in group Ia and 30% (6 out of 20) in group Ib and no viral DNA was detected in the controls (P value=0.001). Although 42.3% (11 out of 26) of children with β thalassemia major had a detectable level of antiparvovirus B19 virus IgG antibodies, only (23.1%) (6 out of 26) of them had B19 DNA. Anti-parvovirus B19 IgG antibodies were detected in 4 children out of 5 children of sickle cell anemia (80%) but the the prevalence of Parvovirus B19 DNA was 20% among them. Conclusion: Measures to keep away from iatrogenic and nosocomial infection transmission should be implemented including screening of donated blood for parvovirus B19 especially blood given to patients with blood disorders. Recommendation: Data from this study support the need for introduction of an approved vaccine that mainly protects children with chronic hemolytic anemia against that infection.


Sign in / Sign up

Export Citation Format

Share Document