Identification of a novel alpha1-antitrypsin variant

Seynes, Camille de; Ged, Cécile; Verneuil, Hubert de; Chollet, N.; Balduyck, Malika

doi:10.1016/j.rmcr.2016.11.008

Cited by 3 publications

(2 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although detecting rare/novel mutations can be challenging, recent sequencing techniques (NGS) should be employed when standard PCR and IEF tests suggest a normal genotype in patients with low/normal AAT levels. Gene sequencing techniques are able to detect rare/novel genotypes, and in some cases, can help to determine the most suitable course of treatment for patients with AATD [ 3 ]. Nevertheless, it should be noted that sequencing techniques are generally expensive to run and less widely available in general laboratory/clinic settings than more basic tests.…”

Section: Discussionmentioning

confidence: 99%

“…The primary function of AAT is to regulate serine proteases and protect the lungs from elastolytic damage by inhibiting the proteolytic enzyme neutrophil elastase [ 2 ]. Sequence variants of the SERPINA1 gene can result in low serum levels of AAT or subtle structural changes to the protein that reduce its functionality [ 3 ]. This deficit in functional AAT results in Alpha 1 Antitrypsin Deficiency (AATD), a condition associated with lung tissue destruction, emphysema and liver disease [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical presentations of four patients with rare Alpha 1 Antitrypsin variants identified in a single US center

Kueppers

2021

Respiratory Medicine Case Reports

View full text Add to dashboard Cite

Alpha 1 Antitrypsin Deficiency (AATD) is a rare condition primarily associated with lung complications and liver disease. As disease symptoms are similar to those in other respiratory conditions, patients generally experience long delays before receiving an accurate diagnosis and treatment. AATD results from mutations in the SERPINA1 gene that encodes Alpha 1 Antitrypsin (AAT). Over 500 single-nucleotide variants have been reported in mutation databases; however, there is increasing interest in the clinical significance of rare and novel SERPINA1 variants. In this case series of four patients from a single US center, next-generation sequencing (NGS) was used to guide AATD diagnosis. Four distinct rare variants of SERPINA1 (P289S; I50N; E204K; H262Y) were identified, three of which were found in patients with advanced chronic obstructive pulmonary disease (COPD)/emphysema. Computational modeling predicted these mutations to have potentially deleterious effects, a finding supported by AAT levels that were comparable with those seen in individuals heterozygous for the most common deficiency allele (PI*MZ). The remaining mutation (E204K) was found in a patient with a cerebral aneurysm; potential links between SERPINA1 variants and neurological conditions, such as cerebral aneurysm and arterial dissections, have been previously reported in individuals with heterozygous AATD phenotypes (PI*MS and PI*MZ). Novel and rare variants, often not detected by basic AATD diagnostic tests, have the potential to contribute to the development of COPD and emphysema. Detection of these variants can be enhanced by NGS, and modeling techniques can help determine if variants are pathogenic, thereby enabling a quicker, more accurate AATD diagnosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical presentations of four patients with rare Alpha 1 Antitrypsin variants identified in a single US center

Kueppers

2021

Respiratory Medicine Case Reports

View full text Add to dashboard Cite

show abstract

Novel SERPINA1 Alleles Identified Through a Large Alpha-1 Antitrypsin Deficiency Screening Program and Review of Known Variants

Wiesemann¹,

Oshins²,

Flagg³

et al. 2023

J COPD F

View full text Add to dashboard Cite

show abstract

Serpin Family A Member 1 Is Prognostic and Involved in Immunological Regulation in Human Cancers

Kuai

Zhang

et al. 2023

IJMS

View full text Add to dashboard Cite

Serpin family A member 1 (SERPINA1) encodes a protease inhibitor participating in many human diseases, but its value in immunoregulation and prognosis of human cancers remains unclear. In this study, through comprehensive analysis of data from The Cancer Genome Atlas (TCGA) datasets, we found that SERPINA1 was dysregulated in many cancers compared with normal tissues. SERPINA1 expression was significantly associated with prognosis, immune subtype, molecular subtype, immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), and the estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) score. There was a strong connection between SERPINA1 expression and tumor-infiltrating lymphocytes, and SERPINA1 showed significant relation to gene markers of immune cells in digestive tumors. Fluorescence-based multiplex immunohistochemistry confirmed that SERPINA1 protein expression was related to clinicopathologic features and immune infiltrates in hepatic cancer. This study suggests that SERPINA can potentially serve as a novel biomarker for cancer prognosis and immunotherapy.

show abstract

Identification of a novel alpha1-antitrypsin variant

Cited by 3 publications

References 17 publications

Clinical presentations of four patients with rare Alpha 1 Antitrypsin variants identified in a single US center

Clinical presentations of four patients with rare Alpha 1 Antitrypsin variants identified in a single US center

Novel SERPINA1 Alleles Identified Through a Large Alpha-1 Antitrypsin Deficiency Screening Program and Review of Known Variants

Serpin Family A Member 1 Is Prognostic and Involved in Immunological Regulation in Human Cancers

Contact Info

Product

Resources

About