Phenotypic features in patients with cystic fibrosis with L138ins (p.Leu138dup) mutation

Петрова, Н. В.; Kashirskaya, N.; Vasilyeva, Tatyana A.; Voronkova, A.; Kondratieva, E.; Шерман, В. Д.; Новоселова, О. Г.; Krasovskiy, S.; Chernyak, Alexander V.; Amelina, E.; Гинтер, Е. К.; Kutsev, Sergey I.; Зинченко, Р. А.

doi:10.24110/0031-403x-2017-96-6-64-72

Cited by 4 publications

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“…The L138ins variant (c.413_415dupTAC, p.(Leu138dup)) is a duplication of three CTAnucleotides in exon 4 of the CFTR gene. This type of genetic variant belongs to small insertions/deletions that do not change the reading frame, also known as in-frame insertions/deletions [16,19]. This nucleotide sequence variant results in a leucine duplication (CTA codon) at position 138, which adds an amino acid residue to CFTR protein molecule.…”

Section: Discussionmentioning

confidence: 99%

“…This nucleotide sequence variant results in a leucine duplication (CTA codon) at position 138, which adds an amino acid residue to CFTR protein molecule. This position is located in the second motif of the CFTR protein penetrating the membrane, the first membrane-bound domain (MSD1) involved in the formation of the pore of the chlorine channel, which violates the properties of the conductivity of the chlorine channel (IV-V classes of pathogenic effect on the CFTR protein) [19].…”

Section: Discussionmentioning

confidence: 99%

“…The patient had the L138ins/5T genotype, preserved pancreatic function, no lung involvement, and normal sweat chloride (less than 60 mmol/L). Currently, the L138ins variant (c.413_415dupTAC, p.(Leu138dup)) is defined as pathogenic, causing CF-causing variant of the CFTR gene with mild clinical signs [19,20].…”

Section: Discussionmentioning

confidence: 99%

“…They have lower sweat chloride levels and a later age at diagnosis of CF, they more often have a higher FEV1 index, their nutritional status is better due to preserved exocrine pancreatic function. F508del/L138ins compound heterozygotes do not have meconium ileus, CF-associated diabetes mellitus, severe liver damage and chronic Pseudomonas aeruginosa (Pseudomonas aeruginosa) infection is much less common than those who are homozygous for the most common pathogenic CFTR gene variant, F508del [19,20].…”

Section: Discussionmentioning

confidence: 99%

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L138ins Variant of the CFTR Gene in Russian Infertile Men

Черных

Sorokina

et al. 2023

Genes

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(1) Introduction: Pathogenic variants in the CFTR (Cystic Fibrosis Transmembrane conductance Regulator, OMIM: 602421) gene cause Cystic Fibrosis (CF, OMIM: 219700) and CF-related disorders (CF-RD), often accompanied by obstructive azoospermia due to congenital bilateral aplasia of vas deferens (CBAVD, OMIM: 277180) in male patients. The L138ins (c.413_415dup; p. (Leu138dup)) is a mild variant in the CFTR gene that is relatively common among CF-patients in Slavic populations. The frequency of this variant in Russian infertile men has not been sufficiently studied; (2) Materials and Methods: The sample consisted of 6033 Russian infertile men. The patients were tested for 22 common in Russian populations pathogenic variants of the CFTR gene and the IVS9Tn-polymorphic locus of the intron 9. Molecular-genetic studies were performed using amplified fragment length polymorphism (AFLP-PCR), multiplex ligation-dependent probe amplification (MLPA), and nested PCR (for analysis of the IVS9Tn-polymorphic locus); (3) Results: Pathogenic variants in the CFTR were detected in 3.9% of patients. The most frequent variants were F508del and CFTRdele2.3(21kb), accounted for 61.0% and 7.1% of detected variants, respectively. The L138ins variant was detected in 17 (0.28%) individuals: one of them was homozygous, 10 patients were heterozygous, and 6 patients were compound-heterozygous (F508del/L138ins, n = 4; L138ins/N1303K, n = 1; L138ins/5T, n = 1). Two pathogenic CF-causing variants in the CFTR gene were detected in 8 patients, including 7 compound heterozygous (F508del/L138ins, n = 4; F508del/N1303K, n = 1; 2184insA/E92K, n = 1; 3849+10kbC>T/E92K, n = 1) and one homozygous (L138ins/L138ins). The L138ins variant was found in 7 out of 16 (43.75%) chromosomes in six of these patients. The most common pathogenic variant, F508del, was identified in five out of them, in 5 of 16 (31.25%) chromosomes. The allele frequency (AF) of the L138ins variant in the sample has been found to be 0.0014.; (4) Conclusions: The L138ins variant of the CFTR gene is the third most common variant after F508del and CFTRdele2.3(kb) among Russian infertile men.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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L138ins Variant of the CFTR Gene in Russian Infertile Men

Черных

Sorokina

et al. 2023

Genes

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“…In regions with a predominantly Russian population, the most frequent are the F508del (49–65%) and CFTRdele2,3 (2–7%) variants [ 7 , 11 ]. A number of variants that are relatively frequent in Russian patients are not found in the other regions of the world [ 12 , 13 , 14 ], e.g., L138ins [ 11 , 15 ], W1282R [ 7 , 11 ], and 3272-16T>A [ 11 , 16 ]. Their frequencies according to the RCFPR 2018 database are 1.35%, 0.52%, and 0.34%, respectively [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical Presentation of the c.3844T>C (p.Trp1282Arg, W1282R) Variant in Russian Cystic Fibrosis Patients

Петрова

Kashirskaya

Krasovskiy

et al. 2020

Genes

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The goal was to study the phenotypic manifestations of c.3844T>C (p.Trp1282Arg, W1282R) variant, a CF-causing mutation, in patients from the Russian Federation. Clinical manifestations and complications (the age at CF diagnosis, sweat test, pancreatic status, lung function, microbial infection, body mass index (BMI), the presence of meconium ileus (MI), diabetes, and severe liver disease) were compared in four groups: group 1—patients carrying c.3844T>C and severe class I or II variant in trans; group 2—3849+10kbC>T/F508del patients; group 3—F508del/F508del patients; and group 4—patients with W1282R and “mild” variant in trans. Based on the analyses, W1282R with class I or II variant in trans appears to cause at least as severe CF symptoms as F508del homozygotes as reflected in the early age of diagnosis, high sweat chloride concentration, insufficient pancreatic function, and low lung function, in contrast to 3849+10kbC-T/F508del compound heterozygotes having milder clinical phenotypes. The W1282R pathogenic variant is seemed to lead to severe disease phenotype with pancreatic insufficiency similarly to the F508del homozygous genotype.

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Characteristics of the L138ins (p.Leu138dup) mutation in Russian cystic fibrosis patients

Петрова

Kashirskaya

Vasilyeva

et al. 2020

JMS

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The L138ins mutation, found in Russian cystic fibrosis (CF) patients, is a duplication of three nucleotides (CTA) in exon 4 of the CFTR gene and is categorised as a small in-frame insertion/deletion. As a result, the CFTR protein molecule elongates by one amino acid residue, leucine, at position 138 (codon 138 (CTA)). In accordance with the new nomenclature, it should be called c.411_412insCTA (p.Leu138dup). The c.411_412insCTA (p.Leu138dup, L138ins) mutation is found in CF patients of Slavic origin (Russians, Ukrainians) and has been linked to a single haplotype of the intragenic DNA markers IVS1CA-IVS6aGATT-IVS8CA-IVS17bCA - 22-7-16-13.

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Phenotypic features in patients with cystic fibrosis with L138ins (p.Leu138dup) mutation

Cited by 4 publications

References 0 publications

L138ins Variant of the CFTR Gene in Russian Infertile Men

L138ins Variant of the CFTR Gene in Russian Infertile Men

Clinical Presentation of the c.3844T>C (p.Trp1282Arg, W1282R) Variant in Russian Cystic Fibrosis Patients

Characteristics of the L138ins (p.Leu138dup) mutation in Russian cystic fibrosis patients

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