scholarly journals Characterization of a Cohort of Patients With LIG4 Deficiency Reveals the Founder Effect of p.R278L, Unique to the Chinese Population

2021 ◽  
Vol 12 ◽  
Author(s):  
Xianze Luo ◽  
Qing Liu ◽  
Jinqiu Jiang ◽  
Wenjing Tang ◽  
Yuan Ding ◽  
...  
Keyword(s):  
Founder Effect ◽  
Genetic Diagnosis ◽  
Primary Immunodeficiency Disease ◽  
Chinese Patients ◽  
Mutation Site ◽  
Ligase Iv ◽  
Immunodeficiency Disease ◽  
Migration Pathways ◽  
Clinical Problems

DNA ligase IV (LIG4) deficiency is an extremely rare autosomal recessive primary immunodeficiency disease caused by mutations in LIG4. Patients suffer from a broad spectrum of clinical problems, including microcephaly, growth retardation, developmental delay, dysmorphic facial features, combined immunodeficiency, and a predisposition to autoimmune diseases and malignancy. In this study, the clinical, molecular, and immunological characteristics of 15 Chinese patients with LIG4 deficiency are summarized in detail. p.R278L (c.833G>T) is a unique mutation site present in the majority of Chinese cases. We conducted pedigree and haplotype analyses to examine the founder effect of this mutation site in China. This suggests that implementation of protocols for genetic diagnosis and for genetic counseling of affected pedigrees is essential. Also, the search might help determine the migration pathways of populations with Asian ancestry.

scholarly journals The use of CRISPR for variant specificity in the genetic diagnosis of primary immunodeficiency disease (PID)

2019 ◽  
Author(s):  
Tiffeney Mann ◽  
Amy Smith ◽  
Sarah Spencer ◽  
Alasdair Russell ◽  
James Thaventhiran
Keyword(s):  
T Lymphocytes ◽  
Genetic Variants ◽  
Genetic Diagnosis ◽  
Primary Immunodeficiency Disease ◽  
Model Systems ◽  
Deficient Patient ◽  
Uncertain Significance ◽  
Immunodeficiency Disease ◽  
Variant Assessment ◽  
Generation Sequencing

ABSTRACTThe functional validation of genetic variants of uncertain significance (VUS) found in PID patients by next-generation sequencing has traditionally been carried out in model systems that are susceptible to artefact. We use CRISPR correction of primary human T lymphocytes to demonstrate that a specific variant in an IL-6R deficient patient is causative for their condition. This methodology can be adapted and used for variant assessment of the heterogeneous genetic defects that affect T lymphocytes in PID.

Chronic granulomatous disease due to different mutations in patients from the same consanguineous extended family

2018 ◽  
Vol 5 (2) ◽  
pp. 57-60
Author(s):  
Arnon Broides ◽  
Ronit Gavrieli ◽  
Jacov Levy ◽  
Rachel Levy ◽  
Nurit Hadad ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
Primary Immunodeficiency ◽  
Genetic Diagnosis ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Primary Immunodeficiency Disease ◽  
Genetic Mutation ◽  
Reasonable Assumption ◽  
Granulomatous Disease ◽  
Genetic Causes ◽  
Immunodeficiency Disease

Chronic granulomatous disease is a primary immunodeficiency disease caused by a genetic mutation in any of the 5 genes encoding the different components of the Nicotinamide Adenine Dinucleotide Phosphate reduced (NADPH)-Oxidase enzyme complex. Since primary immunodeficiency diseases are considered to be rare diseases, the genetic diagnosis of a certain primary immunodeficiency leads to the reasonable assumption that all patients with the same disease within the same family will have the same genetic mutation. We report 2 patients with chronic granulomatous disease from the same extended consanguineous family who had different genetic causes of their disease. Therefore, it is crucial to obtain a definitive genetic diagnosis of primary immunodeficiency disease even in patients from the same family, where the same genetic diagnosis is presumed to be the cause of the disease. Statement of novelty: Genetic causes of chronic granulomatous disease may be different in patients from the same family.

scholarly journals Prevalent Pathogenic Variants of ATP7B in Chinese Patients with Wilson’s Disease: Geographical Distribution and Founder Effect

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 336
Author(s):  
Guo-Min Yang ◽  
Rou-Min Wang ◽  
Nan Xia ◽  
Zi-Wei Zheng ◽  
Yi Dong ◽  
...  
Keyword(s):  
Geographical Distribution ◽  
Founder Effect ◽  
Wilson’S Disease ◽  
Autosomal Recessive Disorder ◽  
Wilson's Disease ◽  
Chinese Patients ◽  
Mainland Chinese ◽  
Pathogenic Variants ◽  
Specific Distribution ◽  
The Common

Wilson’s disease (WD) is an autosomal recessive disorder caused by ATP7B pathogenic variants. This study aimed to show the geographical distribution and haplotype spectrum of three prevalent pathogenic variants (p.R778L, p.P992L, p.T935M) in mainland Chinese population and clarify whether the founder effect may account for their origins. We firstly summarized the frequency and geographical distribution of p.R778L, p.P992L and p.T935M in 715 WD patients. Then, to construct haplotypes associated with the three variants, Sanger sequencing and microsatellite typing at three dinucleotide-repeat markers (D13S314, D13S301, D13S316) flanking the ATP7B gene were performed in 102 WD families. An obvious regional-specific distribution feature was found in p.T935M. Linkage disequilibrium at the three markers was shown in all the three variants and we found the common haplotypes specific for p.R778L, p.P992L and p.T935M respectively, represented successively by 10-7-7, 10-9-5 and 12-4-8, which all exhibited great significance vs. the control chromosomes (p < 0.01). Meanwhile, haplotypes for the three variants differed from the studies in other regions to some extent. The common haplotypes we found indicate that three prevalent pathogenic variants emerge due to the founder effect. Furthermore, the study contributes to expand our knowledge of the genetic diversity of WD from a cross-regional perspective.

scholarly journals OP0102 GENE SCREENING OF PRIMARY IMMUNODEFICIENCY DISEASES IN PATIENTS WITH JUVENILE SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 66.2-66
Author(s):  
J. LI ◽  
W. Wang ◽  
C. Y. Wang ◽  
J. Y. Pan ◽  
H. Song
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Primary Immunodeficiency ◽  
Lupus Erythematosus ◽  
Gene Sequencing ◽  
Primary Immunodeficiency Disease ◽  
Type I ◽  
Cmv Infection ◽  
Systemic Lupus ◽  
Genetic Tests ◽  
Immunodeficiency Disease

Background:Systemic lupus erythematosus (SLE) is one of the most common auto-immune diseases in childhood. Primary immunodeficiency disease (PID) patients may present or combine with autoimmune diseases.Objectives:This study aimed to perform gene sequencing via high-throughput sequencing technology in a series of Chinese pediatric SLE patients, and investigate the concomitant situation of PIDs and SLE. Gene sequencing results may help clarify the pathogenesis of SLE.Methods:This was a retrospective case series of SLE children who referred to the Peking Union Medical College Hospital between 01/2016 and 09/2019. Genetic tests were performed in patients who met the inclusion criteria. We then collected demographic, clinical, and treatment information of all involved patients. Descriptive statistics were used.Results:Seventy-one patients were finally included (eighteen boys and fifty-three girls). The median age at the time of disease onset was 9.5 (range, 3-15) years. It is notable that five patients experienced their first attack before the age of five. Twenty-seven patients showed a persistent increase in ESR during treatment, while thirteen cases presented with repeated CMV infection, thirty-four cases with persistent low complement levels, seven with basal ganglia calcification showed in skull CT or MRI, four with special type of rash (i.e., frostbite-like rash, discoid erythema, reticular erythema), two with obvious hepatosplenomegaly, and one case with type I diabetes. Gene sequencing results showed that about ten patients combine with primary immunodeficiency disease, including Aicardi-Goutières Syndrome (AGS) (n=4), Spondyloenchondro-dysplasia with immune dysregulation (SPENCDI) (n=1), STING-associated vasculopathy with onset in infancy (SAVI) (n=1), lysinuric protein intolerance (LPI) (n=1), Ras-associated autoimmune leukoproliferative disorder (RALD) (n=2).Conclusion:SLE patients who present atypical or refractory manifestations should attach importance to the existence of primary immunodeficiency disease. Genetic tests are recommended for patients with early-onset SLE, especially those with recurrent frostbite-like rash or persistent CMV infection since childhood.References:[1]T Tarr, B Dérfalvi, N Győri, et al. Similarities and differences between pediatric and adult patients with systemic lupus erythematosus[J]. Lupus. 2015, 24: 796–803.[2]Gupta S, Louis A G. Tolerance and Autoimmunity in Primary Immunodeficiency Disease: a Comprehensive Review[J]. Clinical Reviews in Allergy & Immunology, 2013, 45(2):162-169.Disclosure of Interests:None declared

scholarly journals P-194. Characterization of ΔF508/F508C embryos for preimplantation genetic diagnosis

1999 ◽  
Vol 14 (Suppl_3) ◽  
pp. 238-238
Author(s):  
C. Giménez ◽  
N. Pérez ◽  
J. Egozcue ◽  
F. Vidal ◽  
M. Boada ◽  
...  
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Genetic Diagnosis

scholarly journals Genotype Characterization of Human Hydatid Cyst Isolates From Patients in Karaj, Iran, Using COX1 Gene Sequence

2019 ◽  
Vol 7 (1) ◽  
pp. 27-29
Author(s):  
Maryam Salimi ◽  
Abolfazl Miahipour ◽  
Mohammad Zibaei ◽  
Sasan Rezaie
Keyword(s):  
Hydatid Cyst ◽  
Gene Sequence ◽  
Cox1 Gene ◽  
Zoonotic Infection ◽  
Pcr Assay ◽  
Genetic Characteristics ◽  
Control And Prevention ◽  
Polymerase Chain ◽  
Clinical Problems

Background: Cystic echinococcosis is a main zoonotic infection. It can cause serious clinical problems for human health around the world. Genotypic specification of Echinococcus granulosus in human is important due to control and prevention programs. Objective: In this investigation, genetic characteristics of human isolates of E. granulosus in Karaj, Iran, were studied. Materials and Methods: In this review, 3 isolates of surgically removed hydatid cysts were obtained from patients in Shahid Madani hospital, Karaj, Iran in 2014. DNA was extracted from the protoscolex of the cyst, and polymerase chain reaction (PCR) assay was done on the COX1 gene. Results: DNA fragments were sequenced and the results were aligned and analyzed. Among the isolates, 3 (100%) were E. granulosus (G1) strain. Conclusion: The G1 genotype was the most superior strain from human isolates of hydatid cyst in Karaj.

scholarly journals Clinical and Immunological Features of Human BCL10 Deficiency

2021 ◽  
Author(s):  
Blanca Garcia Solis ◽  
Ana Van Den Rym ◽  
Jareb J. Pérez-Caraballo ◽  
Abdulwahab Al –Ayoubi ◽  
Lazaro Lorenzo ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Respiratory Infections ◽  
Genetic Diagnosis ◽  
Additional Patient ◽  
Hematopoietic Stem ◽  
Recommended Treatment ◽  
History Of ◽  
Different Populations ◽  
Human Immune

Abstract The CARD-BCL10-MALT1 (CBM) complex is critical for the proper assembly of human immune responses. The clinical and immunological consequences of deficiencies in some of its components such as CARD9, CARD11, and MALT1 have been elucidated in detail. However, the scarcity of BCL10 deficient patients prevented gaining that knowledge for this genetic disease. Only two patients with BCL10 deficiency have been reported to date. Here we describe in more depth an additional patient with autosomal recessive BCL10 complete deficiency caused by a nonsense mutation that leads to a loss of expression (K63X). Using mass cytometry coupled with unsupervised clustering and machine learning computational methods, we obtained a thorough characterization of the consequences of BCL10 deficiency in different populations of leukocytes. We showed that in addition to the almost absence of memory B and T cells reported before, this patient display a reduction in NK, gdT, Tregs, and TFH cells. The patient suffered from recurrent respiratory infections since early in life, and showed a family history of lethal severe infectious diseases. Fortunately, hematopoietic stem-cell transplantation (HSCT) cured her. Overall, this report highlights the importance of early genetic diagnosis for the management of BCL10 deficient patients and HSCT as the recommended treatment to cured this disease.

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