11 results on '"H. Vahidnezhad"'
Search Results
2. A Novel Homozygote Pathogenic Variant in the DIAPH1 Gene Associated With Seizures, Cortical Blindness, and Microcephaly Syndrome (SCBMS): Report of a Family and Literature Review.
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Esmaeilzadeh E, Biglari S, Mosallaei M, Khorshid HRK, Vahidnezhad H, and Tabatabaiefar MA
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- Humans, Male, Child, Blindness, Cortical genetics, Blindness, Cortical pathology, Syndrome, Pedigree, Phenotype, Mutation, Formins genetics, Homozygote, Microcephaly genetics, Microcephaly pathology, Seizures genetics, Seizures pathology
- Abstract
Objective: Mammalian Diaphanous-Related Formin (mDia1), which is encoded by the DIAPH1 gene, serves as essential for the regulation of cell morphology and cytoskeletal organization. The role of DIAPH1 in brain development has been extensively established. This study aims to evaluate the clinical, neuroradiological, and genetic characteristics of patients with DIAPH1-related disease and determine probable genotype-phenotype relationships., Methods: In the current study, exome sequencing was performed to identify the genetic basis of the clinical presentation in an Iranian 7-year-old boy. Validation of the detected variant was done by Sanger sequencing. Furthermore, we performed a comprehensive review of the literature., Results: Here, we detected a novel homozygous c.1285C> T (p.Gln429*) pathogenic variant in the patient. In silico analysis with prediction software tools identified this variant as a probable source of damage. Twenty cases from seven studies were found after a review of the literature. The patients' main symptoms were a developmental delay, microcephaly, and seizures. The mean age of onset for patients in the group of 20 patients with a known age of onset was 2.3 months (SD = 1.6). Of the variants identified, c.2769del, c.684+1G>A, and c.2332C> T were identified in 72% of the patients., Conclusion: Considering the variant's position in the gene and the encoding protein, a pathogenic effect is predicted for the variant. So, the patient's clinical manifestation is probably caused by this pathogenic variant. Moreover, by studying clinical manifestations in all molecularly confirmed reported cases, provided a comprehensive overview of clinical presentation, and attempted to find a genotype-phenotype correlation., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.) more...
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- 2024
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3. Secondary ACMG and non-ACMG genetic findings in a multiethnic cohort of 16,713 pediatric participants.
- Author
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Saeidian AH, March ME, Youssefian L, Watson DJ, Bhandari E, Wang X, Zhao X, Owen NM, Strong A, Harr MH, Bhoj E, Zackai E, Vahidnezhad H, Gudjonsson JE, Cederbaum SD, Deignan JL, Glessner J, Grody WW, and Hakonarson H more...
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- Humans, Child, Female, Male, Cohort Studies, Genomics methods, Adolescent, Child, Preschool, Genetic Variation genetics, Genetic Predisposition to Disease, Incidental Findings, Genetics, Medical, Black or African American genetics, Infant, Ethnicity genetics, Genetic Testing methods, High-Throughput Nucleotide Sequencing methods
- Abstract
Purpose: Clinical next-generation sequencing is an effective approach for identifying pathogenic sequence variants that are medically actionable for participants and families but are not associated with the participant's primary diagnosis. These variants are called secondary findings (SFs). According to the literature, there is no report of the types and frequencies of SFs in a large pediatric cohort that includes substantial African-American participants. We sought to investigate the types (including American College of Medical Genetics and Genomics [ACMG] and non-ACMG-recommended gene lists), frequencies, and rates of SFs, as well as the effects of SF disclosure on the participants and families of a large pediatric cohort at the Center for Applied Genomics at The Children's Hospital of Philadelphia., Methods: We systematically identified pathogenic (P) and likely pathogenic (LP) variants in established disease-causing genes, adhering to ACMG v3.2 secondary finding guidelines and beyond. For non-ACMG SFs, akin to incidental findings in clinical settings, we utilized a set of criteria focusing on pediatric onset, high penetrance, moderate to severe phenotypes, and the clinical actionability of the variants. This criteria-based approach was applied rather than using a fixed gene list to ensure that the variants identified are likely to affect participant health significantly. To identify and categorize these variants, we used a clinical-grade variant classification standard per ACMG/AMP recommendations; additionally, we conducted a detailed literature search to ensure a comprehensive exploration of potential SFs relevant to pediatric participants., Results: We report a distinctive distribution of 1464 P/LP SF variants in 16,713 participants. There were 427 unique variants in ACMG genes and 265 in non-ACMG genes. The most frequently mutated genes among the ACMG and non-ACMG gene lists were TTR(41.6%) and CHEK2 (7.16%), respectively. Overall, variants of possible medical importance were found in 8.76% of participants in both ACMG (5.81%) and non-ACMG (2.95%) genes., Conclusion: Our study revealed that 8.76% of a large, multiethnic pediatric cohort carried actionable secondary genetic findings, with 5.81% in ACMG genes and 2.95% in non-ACMG genes. These findings emphasize the importance of including diverse populations in genetic research to ensure that all groups benefit from early identification of disease risks. Our results provide a foundation for expanding the ACMG gene list and improving clinical care through early interventions., Competing Interests: Conflict of Interest Hakon Hakonarson and Children’s Hospital of Philadelphia are equity holders in Nobias Therapeutics, developing mitogen-activated protein kinase inhibitor therapy for complex lymphatic anomalies. All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) more...
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- 2024
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4. Healing of Recalcitrant Chronic Ulcers by Hair Follicle-Containing Punch Grafts in Epidermolysis Bullosa.
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Moravvej H, Vahidnezhad H, and Mozafari N
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- 2024
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5. The effect of family structure on the still-missing heritability and genomic prediction accuracy of type 2 diabetes.
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Amiri Roudbar M, Vahedi SM, Jin J, Jahangiri M, Lanjanian H, Habibi D, Masjoudi S, Riahi P, Fateh ST, Neshati F, Zahedi AS, Moazzam-Jazi M, Najd-Hassan-Bonab L, Mousavi SF, Asgarian S, Zarkesh M, Moghaddas MR, Tenesa A, Kazemnejad A, Vahidnezhad H, Hakonarson H, Azizi F, Hedayati M, Daneshpour MS, and Akbarzadeh M more...
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- Humans, Female, Male, Genomics methods, Iran, Models, Genetic, Cohort Studies, Genome-Wide Association Study, Genotype, Case-Control Studies, Middle Aged, Family, Family Structure, Diabetes Mellitus, Type 2 genetics, Pedigree, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide genetics
- Abstract
This study aims to assess the effect of familial structures on the still-missing heritability estimate and prediction accuracy of Type 2 Diabetes (T2D) using pedigree estimated risk values (ERV) and genomic ERV. We used 11,818 individuals (T2D cases: 2,210) with genotype (649,932 SNPs) and pedigree information from the ongoing periodic cohort study of the Iranian population project. We considered three different familial structure scenarios, including (i) all families, (ii) all families with ≥ 1 generation, and (iii) families with ≥ 1 generation in which both case and control individuals are presented. Comprehensive simulation strategies were implemented to quantify the difference between estimates of [Formula: see text] and [Formula: see text]. A proportion of still-missing heritability in T2D could be explained by overestimation of pedigree-based heritability due to the presence of families with individuals having only one of the two disease statuses. Our research findings underscore the significance of including families with only case/control individuals in cohort studies. The presence of such family structures (as observed in scenarios i and ii) contributes to a more accurate estimation of disease heritability, addressing the underestimation that was previously overlooked in prior research. However, when predicting disease risk, the absence of these families (as seen in scenario iii) can yield the highest prediction accuracy and the strongest correlation with Polygenic Risk Scores. Our findings represent the first evidence of the important contribution of familial structure for heritability estimations and genomic prediction studies in T2D., (© 2024. The Author(s).) more...
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- 2024
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6. FLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice.
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Momenilandi M, Lévy R, Sobrino S, Li J, Lagresle-Peyrou C, Esmaeilzadeh H, Fayand A, Le Floc'h C, Guérin A, Della Mina E, Shearer D, Delmonte OM, Yatim A, Mulder K, Mancini M, Rinchai D, Denis A, Neehus AL, Balogh K, Brendle S, Rokni-Zadeh H, Changi-Ashtiani M, Seeleuthner Y, Deswarte C, Bessot B, Cremades C, Materna M, Cederholm A, Ogishi M, Philippot Q, Beganovic O, Ackermann M, Wuyts M, Khan T, Fouéré S, Herms F, Chanal J, Palterer B, Bruneau J, Molina TJ, Leclerc-Mercier S, Prétet JL, Youssefian L, Vahidnezhad H, Parvaneh N, Claeys KG, Schrijvers R, Luka M, Pérot P, Fourgeaud J, Nourrisson C, Poirier P, Jouanguy E, Boisson-Dupuis S, Bustamante J, Notarangelo LD, Christensen N, Landegren N, Abel L, Marr N, Six E, Langlais D, Waterboer T, Ginhoux F, Ma CS, Tangye SG, Meyts I, Lachmann N, Hu J, Shahrooei M, Bossuyt X, Casanova JL, and Béziat V more...
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- Animals, Female, Humans, Male, Mice, B-Lymphocytes metabolism, B-Lymphocytes cytology, Bone Marrow metabolism, Cell Lineage, Dendritic Cells metabolism, Hematopoiesis, Hematopoietic Stem Cells metabolism, Hematopoietic Stem Cells cytology, Langerhans Cells metabolism, Monocytes metabolism, Skin metabolism, Mice, Inbred C57BL, Killer Cells, Natural metabolism, Killer Cells, Natural immunology, Membrane Proteins metabolism, Membrane Proteins genetics
- Abstract
FMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic factor essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) in mice. We describe three humans homozygous for a loss-of-function FLT3LG variant with a history of various recurrent infections, including severe cutaneous warts. The patients' bone marrow (BM) was hypoplastic, with low levels of hematopoietic progenitors, particularly myeloid and B cell precursors. Counts of B cells, monocytes, and DCs were low in the patients' blood, whereas the other blood subsets, including NK cells, were affected only moderately, if at all. The patients had normal counts of Langerhans cells (LCs) and dermal macrophages in the skin but lacked dermal DCs. Thus, FLT3L is required for B cell and DC development in mice and humans. However, unlike its murine counterpart, human FLT3L is required for the development of monocytes but not NK cells., Competing Interests: Declaration of interests J.-L.C. serves on the scientific advisory boards of ADMA Biologics Inc., Kymera Therapeutics, and Elixiron Immunotherapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) more...
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- 2024
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7. DNA repair-related heritable photosensitivity syndromes: Mutation landscape in a multiethnic cohort of 17 multigenerational families with high degree of consanguinity.
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Hozhabrpour A, Mojbafan M, Palizban F, Vahidnezhad F, Talebi S, Amani M, Garshasbi M, Naghavi A, Khalesi R, Mansouri P, Sotoudeh S, Mahmoudi H, Varghaei A, Daneshpazhooh M, Karimi F, Zeinali S, Kalamati E, Uitto J, Youssefian L, and Vahidnezhad H more...
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- Humans, Child, Preschool, Consanguinity, Extended Family, Iran, DNA-Binding Proteins genetics, Mutation, DNA Repair, Xeroderma Pigmentosum Group D Protein, Carrier Proteins, Xeroderma Pigmentosum genetics, Photosensitivity Disorders genetics
- Abstract
Inherited photosensitivity syndromes are a heterogeneous group of genetic skin disorders with tremendous phenotypic variability, characterized by photosensitivity and defective DNA repair, especially nucleotide excision repair. A cohort of 17 Iranian families with heritable photosensitivity syndromes was evaluated to identify their genetic defect. The patients' DNA was analyzed with either whole-exome sequencing or RNA sequencing (RNA-Seq). The interpretations of the genomic results were guided by genome-wide homozygosity mapping. Haplotype analysis was performed for cases with recurrent mutations. RNA-Seq, in addition to mutation detection, was also utilized to confirm the pathogenicity. Thirteen sequence variants, including six previously unreported pathogenic variants, were disclosed in 17 Iranian families, with XPC as the most common mutated gene in 10 families (59%). In one patient, RNA-Seq, as a first-tier diagnostic approach, revealed a non-canonical homozygous germline variant: XPC:c.413-9 T > A. The Sashimi plot showed skipping of exon 4 with dramatic XPC down-expression. Haplotype analysis of XPC:c.2251-1 G>C and XPC:1243 C>T in four families showed common haplotypes of 1.7 Mb and 2.6 Mb, respectively, denoting a founder effect. Lastly, two extremely rare cases were presented in this report: a homozygous UVSSA:c .1990 C>T was disclosed, and ERCC2-related cerebro-oculo-facio-skeletal (COFS) syndrome with an early childhood death. A direct comparison of our data with the results of previously reported cohorts demonstrates the international mutation landscape of DNA repair-related photosensitivity disorders, although population-specific differences were observed., Competing Interests: Declaration of Competing Interest Authors have declared that no conflict of interest exist., (Copyright © 2024 Elsevier B.V. All rights reserved.) more...
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- 2024
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8. RARS1-related hypomyelinating leukodystrophy-9 (HLD-9) in two distinct Iranian families: Case report and literature review.
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Biglari S, Vahidnezhad H, Tabatabaiefar MA, Khorram Khorshid HR, and Esmaeilzadeh E
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- Humans, Infant, Infant, Newborn, Iran, Homozygote, Muscle Spasticity, Amino Acyl-tRNA Synthetases, Intellectual Disability
- Abstract
Background: Hypomyelinating leukodystrophy-9 (HLD-9) is caused by biallelic pathogenic variants in RARS1, which codes for the cytoplasmic tRNA synthetase for arginine (ArgRS). This study aims to evaluate the clinical, neuroradiological, and genetic characteristics of patients with RARS1-related disease and determine probable genotype-phenotype relationships., Methods: We identified three patients with RARS1 homozygous pathogenic variants. Furthermore, we performed a comprehensive review of the literature., Results: Homozygous variants of RARS1 (c.2T>C (p.Met1Thr)) were identified in three patients with HLD-9. Clinical symptoms were severe in all patients. Following the literature review, thirty HLD-9 cases from eight studies were found. The 33 patients' main symptoms were hypomyelination, language delay, and intellectual disability or developmental delay. The mean age of onset for HLD9 in the group of 33 patients with a known age of onset was 5.8 months (SD = 8.1). The interquartile range of age of onset was 0-10 months. Of the 25 variants identified, c.5A>G (p.Asp2Gly) was identified in 11 patients., Conclusion: Pathogenic variants in RARS1 decrease ArgRS activity and cause a wide range of symptoms, from severe, early onset epileptic encephalopathy with brain atrophy to a mild condition with relatively maintained myelination. These symptoms include the classic hypomyelination presentation with nystagmus and spasticity. Furthermore, the pathogenicity of the variation c.2T>C (p.Met1Thr) has been shown., (© 2024 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.) more...
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- 2024
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9. A comprehensive study of mutation and phenotypic heterogeneity of childhood mitochondrial leukodystrophies.
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Hosseinpour S, Razmara E, Heidari M, Rezaei Z, Ashrafi MR, Dehnavi AZ, Kameli R, Bereshneh AH, Vahidnezhad H, Azizimalamiri R, Zamani Z, Pak N, Rasulinezhad M, Mohammadi B, Ghabeli H, Ghafouri M, Mohammadi M, Zamani GR, Badv RS, Saket S, Rabbani B, Mahdieh N, Ahani A, Garshasbi M, and Tavasoli AR more...
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- Child, Humans, Mutation genetics, Corpus Callosum, Mitochondria, DNA, Mitochondrial genetics
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Objective: Mitochondrial leukodystrophies (MLs) are mainly caused by impairments of the mitochondrial respiratory chains. This study reports the mutation and phenotypic spectrum of a cohort of 41 pediatric patients from 39 distinct families with MLs among 320 patients with a molecular diagnosis of leukodystrophies., Methods: This study summarizes the clinical, imaging, and molecular data of these patients for five years., Results: The three most common symptoms were neurologic regression (58.5%), pyramidal signs (58.5%), and extrapyramidal signs (43.9%). Because nuclear DNA mutations are responsible for a high percentage of pediatric MLs, whole exome sequencing was performed on all patients. In total, 39 homozygous variants were detected. Additionally, two previously reported mtDNA variants were identified with different levels of heteroplasmy in two patients. Among 41 mutant alleles, 33 (80.4%) were missense, 4 (9.8%) were frameshift (including 3 deletions and one duplication), and 4 (9.8%) were splicing mutations. Oxidative phosphorylation in 27 cases (65.8%) and mtDNA maintenance pathways in 8 patients (19.5%) were the most commonly affected mitochondrial pathways. In total, 5 novel variants in PDSS1, NDUFB9, FXBL4, SURF1, and NDUSF1 were also detected. In silico analyses showed how each novel variant may contribute to ML pathogenesis., Conclusions: The findings of this study suggest whole-exome sequencing as a strong diagnostic genetic tool to identify the causative variants in pediatric MLs. In comparison between oxidative phosphorylation (OXPHOS) and mtDNA maintenance groups, brain stem and periaqueductal gray matter (PAGM) involvement were more commonly seen in OXPHOS group (P value of 0.002 and 0.009, respectively), and thinning of corpus callosum was observed more frequently in mtDNA maintenance group (P value of 0.042)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.) more...
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- 2024
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10. Whole-Transcriptome Sequencing-Based Profiling of the Cutaneous Virome in Patients with Secondary Immunodeficiency.
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Youssefian L, Saeidian AH, Saffarian Z, Ariamanesh M, Abdollahimajd F, Molkara S, Shahidi-Dadras M, Diab R, Vahidnezhad F, Zeinali S, Béziat V, Jouanguy E, Casanova JL, Uitto J, and Vahidnezhad H
- Abstract
Most viral infections can be self-limited, with no requirement for medical intervention. However, the same viruses can cause severe diseases in patients with compromised immunity due to single-gene diseases, acquired immune deficiency syndrome, or hematologic malignancies or those receiving immunosuppressive drugs. Occasionally, these immunocompromised patients harbor >1 infectious agent, requiring several concomitant diagnostic tests. We have developed, to our knowledge, a previously unreported whole-transcriptome sequencing-based pipeline that allows virome profiling, quantitation, and expression pattern analysis of 926 distinct viruses by sequencing of RNA isolated from a single lesional skin biopsy. This pipeline can also explore host genetics if there is a Mendelian predisposition to infection. We applied this pipeline to 6 Iranian patients with viral-induced skin lesions associated with immune deficiency secondary to HIV, human T-lymphotropic virus 1, chronic lymphocytic leukemia, and post transplant immunosuppression. In 5 cases, definitive human papillomavirus infections were identified, some caused by multiple viral types. In addition to human papillomavirus, coinfection with other viruses (Merkle cell polyomavirus, cytomegalovirus, and human herpesvirus 4) was detected in some lesions. In 1 case, whole-transcriptome sequencing validated the clinical diagnosis of adult T-cell leukemia/lymphoma in a patient with an initial diagnosis of mycosis fungoides/Sézary syndrome. These findings attest to the power of whole-transcriptome sequencing in profiling the cutaneous virome in the context of compromised immunity., (© 2024 The Authors.) more...
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- 2024
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11. Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.
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Biglari S, Moghaddam AS, Tabatabaiefar MA, Sherkat R, Youssefian L, Saeidian AH, Vahidnezhad F, Tsoi LC, Gudjonsson JE, Hakonarson H, Casanova JL, Béziat V, Jouanguy E, and Vahidnezhad H
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- Humans, Child, Preschool, Child, Adolescent, Skin, Syndrome, Membrane Proteins genetics, Guanine Nucleotide Exchange Factors, Papillomavirus Infections complications, Papillomavirus Infections genetics, Warts genetics, Warts complications, Epidermodysplasia Verruciformis genetics, Epidermodysplasia Verruciformis complications
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Purpose: Persistent human papillomavirus infection (PHPVI) causes cutaneous, anogenital, and mucosal warts. Cutaneous warts include common warts, Treeman syndrome, and epidermodysplasia verruciformis, among others. Although more reports of monogenic predisposition to PHPVI have been published with the development of genomic technologies, genetic testing is rarely incorporated into clinical assessments. To encourage broader molecular testing, we compiled a list of the various monogenic etiologies of PHPVI., Methods: We conducted a systematic literature review to determine the genetic, immunological, and clinical characteristics of patients with PHPVI., Results: The inclusion criteria were met by 261 of 40,687 articles. In 842 patients, 83 PHPVI-associated genes were identified, including 42, 6, and 35 genes with strong, moderate, and weak evidence for causality, respectively. Autosomal recessive inheritance predominated (69%). PHPVI onset age was 10.8 ± 8.6 years, with an interquartile range of 5 to 14 years. GATA2,IL2RG,DOCK8, CXCR4, TMC6, TMC8, and CIB1 are the most frequently reported PHPVI-associated genes with strong causality. Most genes (74 out of 83) belong to a catalog of 485 inborn errors of immunity-related genes, and 40 genes (54%) are represented in the nonsyndromic and syndromic combined immunodeficiency categories., Conclusion: PHPVI has at least 83 monogenic etiologies and a genetic diagnosis is essential for effective management., Competing Interests: Conflict of Interest Jean-Laurent Casanova serves on the scientific advisory boards of ADMA Biologics Inc., Kymera Therapeutics, and Elixiron Immunotherapeutics., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2024
- Full Text
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