scholarly journals Acquired Pure Red Cell Aplastic in one of the Monozygotic Twins with Common Variable Immunodeficiency

2021 ◽  
Author(s):  
Li Jing Shen ◽  
Xiao Gao ◽  
Jian Hou ◽  
Yi Ke Wan
Keyword(s):  
Genetic Basis ◽  
Clinical Manifestations ◽  
Monozygotic Twins ◽  
Recurrent Infection ◽  
Signal Pathways ◽  
Red Cell ◽  
Whole Exome ◽  
Neoplastic Disorders ◽  
Immune Defects ◽  
Common Variable

Abstract BackgroundCommon variable immunodeficiency (CVID) is the most prevalent primary immune defects in adults. It has become clear that most cases of CVID have a polygenic rather than a monogenic inheritance. CVID patients are prone to recurrent infection, and an increased incidence of certain autoimmune and neoplastic disorders. Monozygotic twins share identical genetic basis and may serve as a powerful model for study on genetic defects.Case presentationHere, we report a case of monozygotic twins were diagnosed with CVID at their 30s’. They featured a partly similar profile of clinical manifestations, including severe, recurring infections and bone pain. Interestingly, only the elder brother developed pure red cell aplastic (PRCA), and relieved after 5-month’s treatment with 100 mg/d of cyclosporine treatment. Whole-exome sequencing (WES) was utilized to investigate genetic defects.ConclusionsThe results suggest that a combination effect of deleterious variations maybe the cause, such as VDR, NHEJ1, DOCK5, NOD2 and C3, which were predicted by bioinformatics analysis. The potential combinatorial effects in CVID is inferred from their roles in T and B cell signal pathways activation.

scholarly journals Facial cleft? The first case of manitoba‐oculo‐tricho‐anal syndrome with novel mutations in China: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuchen Gu ◽  
Yimin Khoong ◽  
Xin Huang ◽  
Tao Zan
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Manifestations ◽  
Sporadic Case ◽  
Facial Cleft ◽  
Ocular Manifestations ◽  
First Case ◽  
Whole Exome ◽  
Chinese Girl ◽  
Low Prevalence

Abstract Background Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare syndrome with only 27 cases reported worldwide so far, but none was reported in the population of Eastern Asia. Such extremely low prevalence might be contributed by misdiagnosis due to its similarities in ocular manifestations with facial cleft. In our study, we discovered the first case of MOTA syndrome in the population of China, with 2 novel FRAS1 related extracellular matrix 1 (FREM1) gene stop-gain mutations confirmed by whole exome sequencing. Case presentation A 12-year-old Chinese girl presented with facial cleft-like deformities including aberrant hairline, blepharon-coloboma and broad bifid nose since birth. Whole exome sequencing resulted in the identification of 2 novel stop-gain mutations in the FREM1 gene. Diagnosis of MOTA syndrome was then established. Conclusions We discovered the first sporadic case of MOTA syndrome according to clinical manifestations and genetic etiology in the Chinese population. We have identified 2 novel stop-gain mutations in FREM1 gene which further expands the spectrum of mutational seen in the MOTA syndrome. Further research should be conducted for better understanding of its mechanism, establishment of an accurate diagnosis, and eventually the exploitation of a more effective and comprehensive therapeutic intervention for MOTA syndrome.

scholarly journals Genetic Diagnosis Using Whole Exome Sequencing in Common Variable Immunodeficiency

2016 ◽  
Vol 7 ◽  
Author(s):  
Patrick Maffucci ◽  
Charles A. Filion ◽  
Bertrand Boisson ◽  
Yuval Itan ◽  
Lei Shang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Common Variable Immunodeficiency ◽  
Genetic Diagnosis ◽  
Whole Exome ◽  
Common Variable

scholarly journals IS HEMOGLOBIN E GENE WIDELY SPREAD IN THE STATE OF MADHYA PRADESH IN CENTRAL INDIA? EVIDENCE FROM FIVE TYPICAL FAMILIES

2014 ◽  
Vol 6 (1) ◽  
pp. e2014060 ◽  
Author(s):  
R S Balgir
Keyword(s):  
Sickle Cell ◽  
Clinical Manifestations ◽  
Central India ◽  
Madhya Pradesh ◽  
Red Cell ◽  
Hemoglobin E ◽  
Vulnerable People ◽  
Hb E ◽  
Double Heterozygosity ◽  
First Time

Background: Red cell inherited hemoglobin anomalies are commonly encountered in the central region of India. These cause a public health concern due to high degree of morbidity, mortality, and fetal loss in the backward, underprivileged, and vulnerable people. Purpose: To report five typical families of hemoglobin E disorders identified for the first time in the state of Madhya Pradesh from central India. Methods: Out of a total of 445 couples/families (excluding the present study) with 1526 persons (848 males and 678 females) referred from a tertiary hospital in central India for investigations of anemia/hemoglobinopathies during the period from March 2010 to February 2014, we came across five typical rare couples/families of hemoglobin E disorders worthy of detailed investigations. Laboratory investigations were carried out following the standard procedures after cross checking for quality control from time to time. Results: For the first time, we have encountered nine cases of heterozygous hemoglobin E trait, two members with hemoglobin E-β-thalassemia (double heterozygosity), two cases of sickle cell-hemoglobin E disease (double heterozygosity), and none with homozygous hemoglobin E. Cases  of hemoglobin E trait, hemoglobin E-β-thalassemia, sickle cell-β-thalassemia and sickle cell-E disease showed moderate to severe anemia, and target cells, and reduced values of red cell indices like RBC, Hb level, HCT, MCV, MCH and MCHC, representing abnormal hematological profile and clinical manifestations before blood transfusion. Conclusions: Double heterozygosity for hemoglobinopathies such as occurrence of β-thalassemia mutation with structurally abnormal hemoglobins (Hb S and Hb E) is a rare entity, but occurs with severe clinical manifestations only in those areas or communities where these are highly prevalent, testifying the migrations and genetic admixture. Distribution of hemoglobin E and β-thalassemia in different districts of Madhya Pradesh indicates that abnormal Hb E gene has wide spread and needs prevention for the rehabilitation of vulnerable people in central India. 

scholarly journals A de novo variant in CASK gene causing intellectual disability and brain hypoplasia: A Case Report and Literature Review

2021 ◽  
Author(s):  
Ying Zhang ◽  
Yanyan Nie ◽  
Yu Mu ◽  
Jie Zheng ◽  
Xiaowei Xu ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mental Disorders ◽  
De Novo ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
De Novo Mutation ◽  
Loss Of Function ◽  
Bioinformatics Analyses ◽  
Whole Exome ◽  
De Novo Variant

Abstract Background：The pathogenic variation of CASK gene can cause CASK related mental disorders. The main clinical manifestations are microcephaly with pontine and cerebellar hypoplasia, X-linked mental disorders with or without nystagmus and FG syndrome. The main pathogenic mechanism is the loss of function of related protein caused by mutation. We reported a Chinese male newborn with a de novo variant in CASK gene. Case presentation：We present an 18-day-old baby with intellectual disability and brain hypoplasia. Whole-exome sequencing was performed, which detected a hemizygous missense mutation c.764G>A of CASK gene. The mutation changed the 255th amino acid from Arg to His. Software based bioinformatics analyses were conducted to infer its functional effect.Conclusions：In this paper, a de novo mutation of CASK gene was reported. Moreover, a detailed description of all the cases described in the literature is reported.CASK mutations cause a variety of clinical phenotypes. Its diagnosis is difficult due to the lack of typical clinical symptoms. Genetic testing should be performed as early as possible if this disease is suspected. This case provides an important reference for the diagnosis and treatment of future cases.

scholarly journals Pure Red Cell Aplasia with Adult Onset Still’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Nicholas Robillard ◽  
Paul Van Nguyen ◽  
Robert Wistaff ◽  
Mikhael Laskine
Keyword(s):  
Clinical Manifestations ◽  
Pure Red Cell Aplasia ◽  
Adult Onset Still’S Disease ◽  
Red Cell ◽  
Adult Onset ◽  
Still’S Disease ◽  
Red Cell Aplasia ◽  
Still's Disease ◽  
Wide Range ◽  
Adult Onset Still's Disease

Adult Onset Still’s Disease (AOSD) is a rare inflammatory syndrome mostly seen in young adults. Known for its wide range of clinical manifestations, AOSD often presents with nonremitting systemic signs and symptoms. Many rare case associations have been described with AOSD, but only few with pure red cell aplasia (PRCA). We are presenting a fourth known case of a young female adult with AOSD and PRCA in the literature.

Disorders of the red cell membrane

2020 ◽  
pp. 5456-5463
Author(s):  
Patrick G. Gallagher
Keyword(s):  
Cell Membrane ◽  
Clinical Features ◽  
Parvovirus B19 ◽  
Clinical Manifestations ◽  
Peripheral Blood Smear ◽  
Membrane Lipid ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Membrane Lipid Bilayer ◽  
Parvovirus B19 Infection

The integrity of the red cell membrane depends on molecular interactions between proteins and the phospholipid membrane: vertical interactions stabilize the membrane lipid bilayer; horizontal interactions provide resistance against shear stress. Hereditary spherocytosis—affects 1 in 25 000 individuals of northern European descent. There is typically a dominant family history, but the condition is genetically heterogeneous: combined spectrin and ankyrin deficiency is the most common defect observed, followed by band 3 deficiency, isolated spectrin deficiency, and protein 4.2 deficiency. These affect vertical membrane interactions with loss of surface area relative to red cell volume. Clinical features—the key clinical manifestations are anaemia and signs of persistent haemolysis, with jaundice and a marked propensity to gallstones. Complications and treatment—parvovirus B19 infection of erythropoietic precursors may cause acute aplastic crises. Megaloblastic anaemia due to folate deficiency occurs in response to increased requirements during growth and pregnancy, but is preventable with supplementation. Splenectomy can alleviate the anaemia in many patients and reduces the risk of gallstones. Hereditary elliptocytosis—occurs with a frequency of 1 in 2000 to 1 in 4000 worldwide, and is more frequent in parts of Africa. The inheritance is usually dominant, with defects in red cell proteins such as α‎- and β‎-spectrin causing disturbances in horizontal interactions in the erythrocyte membrane. Clinical features, diagnosis, and treatment—most patients are asymptomatic and are typically diagnosed incidentally during testing for unrelated conditions, but about 10% experience haemolysis, anaemia, splenomegaly, and intermittent jaundice. Diagnosis is based on the presence of elliptocytes on a peripheral blood smear. Treatment is rarely required. Other conditions include hereditary pyropoikilocytosis, South-East Asian (or Melanesian) ovalocytosis, stomatocytosis, and acanthocytosis.

scholarly journals AIMP1 Mutation Long-Term Follow-Up, With Decreased Brain N-Acetylaspartic Acid and Secondary Mitochondrial Abnormalities

2019 ◽  
Vol 6 ◽  
pp. 2329048X1982952 ◽  
Author(s):  
Aneal Khan ◽  
Jennifer Bennett ◽  
Morris H. Scantlebury ◽  
Xing-Chang Wei ◽  
Marina Kerr
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Monozygotic Twins ◽  
Trna Synthetase ◽  
Resonance Spectroscopy ◽  
Multifunctional Protein ◽  
Whole Exome ◽  
Long Term Follow Up

Aminoacyl transfer RNA (tRNA) synthetase complex-interacting multifunctional protein I is a noncatalytic component of tRNA multi-synthetase complexes. Although important in joining tRNAs to their cognate amino acids, AIMP1 has several other functions including axonal growth, cytokine activity, and interactions with N-acetylaspartic acid in ribosomal tRNA synthetase complexes. Further, N-acetylaspartic acid donates an aspartate during myelination and is therefore important to axonal integrity. Mutations in AIMP1 can disrupt these functions, as demonstrated in this clinical case study of 2 monozygotic twins, who display congenital opisthotonus, microcephaly, severe developmental delay, and seizures. Whole exome sequencing was used to identify a premature stop codon in the AIMP1 gene (g. 107248613_c.115C>T; p.(Gln39). In the absence of whole exome sequencing, we propose that decreased N-acetylaspartic acid peaks on magnetic resonance spectroscopy could act as a biomarker for AIMP1 mutations.

scholarly journals Cochlear Implantation in a Patient with a Novel POU3F4 Mutation and Incomplete Partition Type-III Malformation

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xiuhua Chao ◽  
Yun Xiao ◽  
Fengguo Zhang ◽  
Jianfen Luo ◽  
Ruijie Wang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implantation ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Bioinformatic Analysis ◽  
Chinese Family ◽  
Whole Exome ◽  
Novel Variant ◽  
Genetic Features ◽  
The Right

Aims. This study is aimed at (1) analyzing the clinical manifestations and genetic features of a novel POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family and (2) reporting the outcomes of cochlear implantation in a patient with this mutation. Methods. A patient who was diagnosed as the IP-III malformation underwent cochlear implantation in our hospital. The genetic analysis was conducted in his family, including the whole-exome sequencing combined with Sanger sequencing and bioinformatic analysis. Clinical features, preoperative auditory and speech performances, and postoperative outcomes of cochlear implant (CI) were assessed on the proband and his family. Results. A novel variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was detected in the family, which was cosegregated with the hearing loss. This variant was absent in 200 normal-hearing persons. The phylogenetic analysis and structure modeling of Pou3f4 protein further confirmed that the novel mutation was pathogenic. The proband underwent cochlear implantation on the right ear at four years old and gained greatly auditory and speech improvement. However, the benefits of the CI declined about three and a half years postoperation. Though the right ear had been reimplanted, the outcomes were still worse than before. Conclusion. A novel frame shift variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was identified in a Chinese family with X-linked inheritance hearing loss. A patient with this mutation and IP-III malformation could get good benefits from CI. However, the outcomes of the cochlear implantation might decline as the patient grows old.

scholarly journals The Genetics of Thoracic Aortic Aneurysms and Dissection: A Clinical Perspective

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 182 ◽  
Author(s):  
Nicolai P. Ostberg ◽  
Mohammad A. Zafar ◽  
Bulat A. Ziganshin ◽  
John A. Elefteriades
Keyword(s):  
Genetic Basis ◽  
Surgical Intervention ◽  
Clinical Manifestations ◽  
Aortic Aneurysms ◽  
Screening Tests ◽  
Cellular Mechanisms ◽  
Biomechanical Stress ◽  
Thoracic Aortic Aneurysms ◽  
Aortic Aneurysm And Dissection ◽  
History Of

Thoracic aortic aneurysm and dissection (TAAD) affects many patients globally and has high mortality rates if undetected. Once thought to be solely a degenerative disease that afflicted the aorta due to high pressure and biomechanical stress, extensive investigation of the heritability and natural history of TAAD has shown a clear genetic basis for the disease. Here, we review both the cellular mechanisms and clinical manifestations of syndromic and non-syndromic TAAD. We particularly focus on genes that have been linked to dissection at diameters <5.0 cm, the current lower bound for surgical intervention. Genetic screening tests to identify patients with TAAD associated mutations that place them at high risk for dissection are also discussed.

Prune Belly Syndrome and Heart Defect in One of Monozygotic Twins, Following Exposure to Tigan and Bendectin

1985 ◽  
Vol 34 (1-2) ◽  
pp. 101-104 ◽  
Author(s):  
C. Greene ◽  
A. Wilson ◽  
E. Shapira
Keyword(s):  
Congenital Heart Defect ◽  
Congenital Heart ◽  
Monozygotic Twins ◽  
Hla Typing ◽  
Prune Belly Syndrome ◽  
Red Cell ◽  
Review Of The Literature ◽  
Monozygotic Twinning ◽  
Prune Belly ◽  
Heart Defect

AbstractOne of twins was bom with prune belly syndrome and congenital heart defect following exposure to Bendectin and Tigan. Red cell antigens and HLA typing were compatible with monozygosity. The possible associations of the prune belly syndrome to monozygotic twinning or to teratogenic agents is considered in light of this patient and review of the literature.

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