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Results for “Frameshift variant”

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PubMed2026

A PMS2-deficient pediatric high-grade glioma with PI3K-pathway mutations and adjacent developmental venous anomaly suggestive of CMMRD.

PURPOSE: Constitutional mismatch repair deficiency (CMMRD) is a rare hereditary cancer predisposition syndrome that frequently manifests with pediatric high-grade gliomas. However, recognition remains challenging, particularly in the absence of a clear family history. We report a pediatric high-grade glioma with PMS2 deficiency and complex molecular alterations to highlight key diagnostic clues and the importance of routine mismatch repair assessment. METHODS: Clinical, radiological, histopathological, immunohistochemical, and molecular findings of an 8-year-old girl presenting with a high-grade glioma were retrospectively evaluated. Immunohistochemistry included glial and mismatch repair markers. Targeted next-generation sequencing was performed to assess tumor mutational burden and pathogenic variants. RESULTS: Neuroimaging revealed a right frontoparietal mass associated with an adjacent developmental venous anomaly. Histopathology demonstrated a diffuse pediatric-type high-grade glioma with pseudopapillary architecture and marked mitotic activity. Immunohistochemistry showed diffuse p53 overexpression in tumor cells and complete loss of PMS2 expression in both tumor and non-neoplastic cells, supporting constitutional mismatch repair deficiency. Molecular analysis revealed an ultra-hypermutated profile with a tumor mutational burden of 117.4 mutations/Mb, a pathogenic PMS2 frameshift variant, and co-occurring alterations in TP53, PIK3CA, PIK3R1, and PTEN. The presence of PI3K-pathway mutations alongside a venous anomaly suggested a potential biological association. CONCLUSION: This case illustrates the characteristic clinicopathological and molecular features of CMMRD-associated pediatric high-grade glioma and underscores the critical role of routine mismatch repair immunohistochemistry. Integrated histological and genomic evaluation is essential for accurate diagnosis, appropriate genetic counseling, and potential therapeutic implications. Key Points • This case represents a pediatric high-grade glioma arising in the setting of PMS2-related constitutional mismatch repair deficiency (CMMRD). • The tumor exhibited an ultra-hypermutated profile with co-occurring TP53, PIK3CA, PIK3R1, and PTEN mutations. • Loss of PMS2 expression in both tumor and non-neoplastic cells was critical in establishing the diagnosis of CMMRD. • The presence of a developmental venous anomaly may relate to underlying PIK3R1 pathway alterations. • Routine mismatch repair immunohistochemistry is essential in pediatric high-grade gliomas, even in the absence of a family history.

Humans↗

PubMed2006

Identification of Hepta- and Octo-Uridine stretches as sole signals for programmed +1 and -1 ribosomal frameshifting during translation of SARS-CoV ORF 3a variants.

Programmed frameshifting is one of the translational recoding mechanisms that read the genetic code in alternative ways. This process is generally programmed by signals at defined locations in a specific mRNA. In this study, we report the identification of hepta- and octo-uridine stretches as sole signals for programmed +1 and -1 ribosomal frameshifting during translation of severe acute respiratory syndrome coronavirus (SARS-CoV) ORF 3a variants. SARS-CoV ORF 3a encodes a minor structural protein of 274 amino acids. Over the course of cloning and expression of the gene, a mixed population of clones with six, seven, eight and nine T stretches located 14 nt downstream of the initiation codon was found. In vitro and in vivo expression of clones with six, seven and eight Ts, respectively, showed the detection of the full-length 3a protein. Mutagenesis studies led to the identification of the hepta- and octo-uridine stretches as slippery sequences for efficient frameshifting. Interestingly, no stimulatory elements were found in the sequences upstream or downstream of the slippage site. When the hepta- and octo-uridine stretches were used to replace the original slippery sequence of the SARS-CoV ORF 1a and 1b, efficient frameshift events were observed. Furthermore, the efficiencies of frameshifting mediated by the hepta- and octo-uridine stretches were not affected by mutations introduced into a downstream stem-loop structure that totally abolish the frameshift event mediated by the original slippery sequence of ORF 1a and 1b. Taken together, this study identifies the hepta- and octo-uridine stretches that function as sole elements for efficient +1 and -1 ribosomal frameshift events.

Animals↗

PubMed2025

A Genomic Alteration in GATA3 Affects Treatment Responses With a CDK4/6 Inhibitor Collaborating With p18INK4C Expression in Advanced Breast Carcinoma.

Cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) with endocrine therapy benefits patients with hormone receptor-positive, human epidermal growth receptor 2-negative breast carcinomas. However, most tumors develop resistance to CDK4/6i during the course of therapy. Although preclinical studies have proposed molecular mechanisms for the resistance, predictive markers are yet to be discovered. We investigated the tumor molecular profiling in 42 patients with advanced-stage breast carcinoma who received CDK4/6i therapy. The tumors carrying a GATA-binding protein 3 (GATA3) gene mutation, mainly a frameshift variant, showed a better treatment response compared with other tumors. Furthermore, we explored the potential underlying mechanism of this association. To that end, nuclear expression of p18, one of the INK family proteins, was found to be positively associated with the GATA3 mutation, as well as a CDK4/6i treatment response. Therefore, our study suggests that a GATA3 gene mutation, collaborating with p18 protein expression in tumor nuclei, may have a predictive value for CDK4/6i therapy in breast carcinoma.

Humans↗

PubMed2002

Polymorphisms in the ABCC2 (cMOAT/MRP2) gene found in 72 established cell lines derived from Japanese individuals: an association between single nucleotide polymorphisms in the 5'-untranslated region and exon 28.

We found nucleotide variability in the 5'-upstream region and exonic sequences of a gene-encoding canalicular multispecific organic anion transporter/multidrug resistance-associated protein 2 (cMOAT/MRP2) by polymerase chain reaction-based sequencing using genomic DNA from 72 established cell lines derived from 72 Japanese individuals. Four single nucleotide polymorphisms (SNPs) were found in the 5'-untranslational region and 21 in the exonic regions. Of them, 14 were nonsynonymous SNPs. One deletion of seven consecutive adenines resulting in a frameshift variant was also found. Four SNPs, c-24t, g1249a (V417I), c2366t (S789F), and c3972t (I1324I), were the same as those recently reported. A strong association was found between c-24t (5'-untranslated region) and c3972t (exon 28), with the promoter activity of the former worth being compared.

5' Untranslated Regions↗

PubMed2026

Brainstem Disconnection Syndrome in a Patient With Respiratory Failure and Failed Weaning From Oxygen: A Case Report.

BACKGROUND: Brainstem disconnection syndrome (BDS) is an exceedingly rare congenital malformation of the hindbrain characterized by disconnection of the brainstem, often presenting with severe neurological deficits and early neonatal mortality. Whereas previous cases have documented isolated neurological anomalies, this report delineates a distinctive presentation of BDS associated with a specific constellation of multisystem vascular and extracerebral skeletal malformations. CASE PRESENTATION: A 4-month-old female infant, born from a discordant twin pregnancy, exhibited persistent neonatal respiratory failure, failure to wean from oxygen therapy, global tonic-clonic seizures, and severe hypotonia. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the brain demonstrated a complete absence of the pons, a slender tissue cord connecting the midbrain and medulla oblongata, extensive cerebellar hypoplasia, and nonopacification or aplasia of the basilar and distal vertebral arteries. Whole exome sequencing did not reveal any standard inherited neurodevelopmental mutations; however, genomic analysis identified carrier status for a biologically plausible frameshift variant in TMEM67, a gene heavily implicated in ciliary hindbrain morphogenesis. The implementation of targeted supportive care allowed the patient to survive beyond the typical early neonatal period, with the patient remaining alive at a 12-month follow-up. CONCLUSION: This case broadens the known phenotypic and radiological range of BDS by reporting new multilevel skeletal and vascular co-occurring conditions. The notable phenotypic differences seen in this twin pregnancy support the theory of early embryonic vascular disruption. Additionally, the detection of the TMEM67 variant indicates that ciliary gene mutations could be important genetic factors or modifiers in BDS.

MRI neonate↗

PubMed2002

Ghrelin gene: identification of missense variants and a frameshift mutation in extremely obese children and adolescents and healthy normal weight students.

Ghrelin induces obesity via central and peripheral mechanisms. Administration of ghrelin leads to increased food intake and decreased fat utilisation in rodents. Ghrelin levels are decreased in obese individuals. Recently, a polymorphism (Arg-51-Gln) within the ghrelin gene (GHRL) was described to be associated with obesity. We screened the GHRL coding region in 215 extremely obese German Children and adolescents (study group 1) and 93 normal weight students (study group 2) by single strand conformation polymorphism analysis (SSCP). We found the two previously described single nucleotide polymorphisms (SNP: Arg-51-Gln and Leu-72-Met) in similar frequencies in study groups 1 and 2 (allele frequencies were: 0.019 and 0.016 for the 51-Gln allele and 0.091 and 0.086 for the 72-Met allele, respectively). Hence, we could not confirm the previous finding. Additionally, two novel variants were identified within the coding region: (1) We detected one healthy normal weight individual with a frameshift mutation (2bp deletion at codon 34). This frameshift mutation affects the coding region of the mature ghrelin. Hence, it is highly likely that the normal weight student is haplo-insufficient for ghrelin. (2) An A to T transversion leads to an amino acid exchange from Gln to Leu at amino acid position 90. The frequency of the 90-Leu allele was significantly higher in the extremely obese children and adolescents (0.063) than in the normal weight students (0.016; nominal p = 0.011). Additionally, we genotyped 134 underweight students and 44 normal weight adults for this SNP. Genotype frequencies were similar in extremely obese children and adolescents, underweight students and normal weight adults (p > 0.8). In conclusion, we identified four sequence variants in the coding region of the ghrelin gene in individuals belonging to different weight extremes. A frameshift mutation was detected in a normal weight individual. None of the variants seem to influence weight regulation.

Adolescent↗

PubMed2002

A common frameshift mutation and other variants in GJB4 (connexin 30.3): Analysis of hearing impairment families.

Mutations in GJB1, GJB2, GJB3 and GJB6 are involved in hearing impairment. GJB2, GJB3 and GJB6 are also mutated in patients with hyperproliferative skin disorders. The human GJB4 gene has been deduced in silico and a mutation in a family with erythrokeratodermia variabilis has been reported. We describe here the analysis of the GJB4 gene in hearing impairment patients and control subjects. We have identified a common (4%) frameshift mutation (154del4) in GJB4 in both affected and hearing subjects, one patient being homozygous for the mutation. We have also detected five amino acid variants (R103C, R124Q, R160C, C169W and E204A) in individuals that have not skin disorders. While mutation 154del4 is not associated with hearing impairment the involvement of some of the amino acid variants detected here is uncertain. These GJB4 variants should help to define the putative role of connexin 30.3 in both skin disorders and hearing impairment.

Amino Acid Sequence↗

PubMed1999

Human lymphocytes express hGH-N gene transcripts of 22kDa, 20kDa and minor forms of GH, but not hGH-V gene.

Expression of human growth hormone (hGH) in lymphocytes was examined by reverse transcription polymerase chain reaction (RT-PCR) in five normal subjects. Transcripts of hGH-N gene, but not hGH-V gene, were detected. Sequence analysis revealed four kinds of transcripts: 22kDa GH, 20kDa GH and two other forms of variant GH. The 20kDa GH transcript was generated by alternative splicing within exon 3, resulting in a 45bp deletion. One of the variant GH transcripts was also generated by alternative splicing within exon 3, but at a different site, resulting in a 73bp deletion. Because of a frameshift, this variant GH transcript may encode a 6.6kDa protein (truncated GH) that structurally differs from that of 22kDa GH after residue 31. In the other variant GH mRNA, exons 3 and 4 were completely skipped. The proportions of expression of 22kDa GH, 20kDa GH and the truncated GH were 60.9+/-13.6 (+/-S.D.)%, 32.7+/-14.1% and 6.4+/-1.1% (n=5), respectively, by comparative RT-PCR. We conclude that human lymphocytes, like the pituitary gland, express hGH-N gene transcripts of mainly 22kDa GH, but also 20kDa GH and minor variant forms of GH.

Adult↗

PubMed1992

Secretion of alpha-1-proteinase inhibitor requires an almost full length molecule.

In the human disease alpha-1-proteinase inhibitor deficiency, some variants of human alpha-1-proteinase inhibitor are not secreted. These secretory variants contain frameshift mutations leading to products with normal amino acid sequences to the points of the mutations followed by short, aberrant C-terminal sequences and then premature termination (Nukiwa, T., Takahashi, H., Brantly, M., Courtney, M., and Crystal, R. (1987) J. Biol. Chem. 262, 11999-12004; Sifers, R. N., Brashears-Macatee, S., Kidd, V. J., Muensch, H., and Woo, S. L. C. (1988) J. Biol. Chem. 263, 7330-7335; Curiel, D., Brantly, M., Curiel, E., Stier, L., and Crystal, R. G. (1989) J. Clin. Invest. 83, 1144-1152). To examine possible causes for lack of secretion of these null variants, we have altered the alpha-1-proteinase inhibitor cDNA to encode a series of abbreviated forms of this protein that retain authentic sequences to the points of truncation. Examination of the fates of these shortened proteins in transiently transfected Cos 1 cells indicates that the aberrant C-terminal sequences in the naturally occurring variants are not responsible for their lack of secretion and show that truncation prior to Pro391 prevents movement from the endoplasmic reticulum to the Golgi apparatus and therefore secretion. These truncated forms of alpha-1-proteinase inhibitor do not form inclusion bodies in the endoplasmic reticulum, rather they are degraded, probably by the pre-Golgi pathway. Our results support the idea that a sequence of at least 391 of the normal 394 residues is essential for the secretion of alpha-1-proteinase inhibitor and suggest that residue 391 plays an especially important role, perhaps in allowing or directing proper folding or as part of a transport signal, in the secretion of this protein.

Cell Line↗

PubMed1999

Mutation screening and genotype:phenotype correlation in familial hypercholesterolaemia.

The aim of this study was to develop a mutation screening protocol for familial hypercholesterolaemia (FH) patients and to assess genotype/phenotype effects in terms of pre-treatment lipid profiles and presentation of tendon xanthomata (TX). A total of 158 families with clinical definitions of possible (120) or definite (38) FH were studied using a tiered screening protocol. Mutations were identified in 52 families, 44 families showing 23 different LDLR gene defects and eight families showing the common Apo B100 gene defect R3500Q. LDLR defects were detected in various regions of the gene with 56% in the LDL binding domain (exons 2-6) and 37% in the EGF precursor homology domain (exons 7-14). The most common mutations were D461N(7), C210X(5), 932delA(5), and C163Y(4). Frameshift mutations accounted for 20% with nonsense 13%, mis-sense 35%, splice 3%, Apo B 13% and 2% large deletion, 13% of clinically definite FH remained undefined. In conclusion, DNA based diagnosis is possible in 79% (30/38) of clinically definite FH families and of the 120 possible FH families at the start of the screening program, 18% (22/120) now have defined mutations. Overall 60 families from the original 158 meet the clinical and/or genetic criteria for definite FH. Tendon xanthomata were present in only 58% (30/52) of genetically defined FH families, thus limiting its use as a strict diagnostic criteria. Families with low density lipoprotein receptor (LDLR) defects present with higher total and LDL cholesterol levels and a higher incidence of TX than do those with the common Apo B variant, and frameshift mutations appear to have the most severe presentation.

Electrophoresis, Agar Gel↗

PubMed2005

Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome: pathological mutations and polymorphisms.

A total of 45 different mutations of methyl-CpG-binding protein 2 gene (MECP2) were identified in 145 of 219 Japanese patients with typical or atypical Rett syndrome (RTT) (66.2%). A missense mutation, T158M was the most common mutation of MECP2, identified in 22 (19.1%) patients, followed by four nonsense mutations, R168X (14.8%), R270X (13.0%), R255X (9.6%), and R294X (6.1%) in 115 patients with classical RTT. Two missense mutations, R133C (33.3%) and R306C (23.3%), and a nonsense mutation, R294X (13.3%), were common in 30 patients with atypical RTT, including the preserved speech variant (PSV). Frameshift mutations due to nucleotide deletion or insertion were identified in 22 patients with MECP2 mutations, and one of them had a 3.6 kb deletion encompassing exons 3 and 4. Three patients with classical RTT had a splicing anomaly. The wide spectrum of phenotypic variability in patients with RTT has been considered to be correlated with the mutation type and location in MECP2, and X-inactivation. However, most patients showed a random X-inactivation pattern evaluated by an androgen receptor gene polymorphism in this study, suggesting that a skewed X-inactivation might not be a main modification factor on clinical phenotypes of RTT. In addition, three new missense mutations, P176R, A378V and T479M, were identified in patients with RTT, but also in healthy Japanese, indicating that these mutations are non-pathogenic in Japanese. Information about rare polymorphic variations is very important for the molecular diagnosis of RTT, although rare polymorphic variants might differ among ethnic groups.

Adolescent↗

PubMed2001

A role for MLH3 in hereditary nonpolyposis colorectal cancer.

We investigated a possible role of the mismatch-repair gene MLH3 in hereditary nonpolyposis colorectal cancer by scanning for mutations in 39 HNPCC families and in 288 patients suspected of having HNPCC. We identified ten different germline MLH3 variants, one frameshift and nine missense mutations, in 12 patients suspected of HNPCC. Three of the 12 also carried a mutation in MSH6.

Base Sequence↗

PubMed1979

Genetic mechanism accounting for precise immunoglobulin domain deletion in a variant of MPC 11 myeloma cells.

A variant of the MPC 11 cell line, M 311, produces a short immunoglobulin heavy chain. When compared with the parental gamma 2b heavy chain, M 311 was found to have a carboxyl terminal deletion comprising the CH3 domain. The COOH-terminal cyanogen bromide (CNBr) cleavage fragment of M 311 is identical to a corresponding segment ofa parental heavy chain CNBr fragment, with the exception of a substitution of asparagine for lysine at the COOH-terminal residue. This observation enabled prediction of both the parental DNA sequence in this region and the genetic mechanism which generated the variant, a frameshift followed by premature termination. This hypothesis is supported by studies of the DNA sequence of the MPC 11 gamma 2b constant region gene.

Animals↗

PubMed2025

Novel compound heterozygous DOCK6 variants expand the mutational spectrum in prenatal diagnosis of Adams-Oliver syndrome 2.

BACKGROUND: Adams-Oliver syndrome (AOS) is a rare developmental disorder, and the DOCK6 gene is an identified AOS gene. This report highlights the prenatal diagnosis of AOS-2 by ultrasonography and genetic testing. METHODS: A growth-restricted fetus with bilateral ventriculomegaly, paraventricular calcifications, and ventricular septal defect underwent trio-whole-exome sequencing (trio-WES). Functional validation of the splice-altering variant was performed via minigene assays and protein structural modeling. RESULTS: Trio-WES revealed compound heterozygous DOCK6 variants: a paternal frameshift (c.3190_3191del; p. Leu1064Valfs60) and a maternal splice-site variant (c.3241-1G > T). Minigene assays demonstrated that c.3241-1G > T caused intron 26 retention (486 bp), introducing a premature termination codon (p. Val1081Glufs37). Structural modeling confirmed the loss of critical DHR2 domains in both truncated proteins. CONCLUSIONS: This study expands the mutational spectrum of DOCK6 and underscores the importance of combining prenatal imaging with functional genomics for early diagnosis of AOS2.

Adult↗

PubMed2026

INPP5K-related muscular dystrophy caused by a novel synonymous splicing variant in a Chinese patient: a case report.

Congenital muscular dystrophies (CMDs) are a genetically heterogeneous group of disorders. Variants in the INPP5K gene, which encodes a phosphoinositide phosphatase, are a rare cause of CMD. The condition is commonly associated with muscle weakness, early-onset cataracts, and intellectual disability, and prior reports have primarily identified missense, frameshift, or deletion variants. We describe the first Chinese case of INPP5K-related muscular dystrophy in a 28-year-old male with a mild phenotype, notably lacking intellectual disability. His presentation included bilateral cataracts at age 5 and adolescent onset limb girdle weakness. Muscle magnetic resonance imaging (MRI) revealed a characteristic pattern of selective fatty infiltration, with severe involvement of gluteal and thigh muscles and striking sparing of the rectus femoris, sartorius, and gracilis. Genetic analysis identified compound heterozygous novel INPP5K variants: a missense c.274C>T, p.(Arg92Cys) and a synonymous c.261G>A, p.(Lys87=) change. Functional studies confirmed the synonymous variant causes aberrant splicing (exon 3 skipping), leading to a frameshift and premature termination p.(Leu52SerfsTer49). According to American College of Medical Genetics and Genomics guidelines, the c.274C>T and c.261G>A variants were classified as likely pathogenic and pathogenic, respectively. This first report of a Chinese patient with INPP5K-related muscular dystrophy broadens both the genetic and clinical spectrum of the disorder. We identify the first disease-causing synonymous variant (via aberrant splicing) and a novel hypomorphic missense variant p.(Arg92Cys), the combination of which explains the attenuated phenotype lacking intellectual disability. Our case highlights the critical role of RNA analysis in diagnosing non-canonical variants and confirms the universal diagnostic relevance of the characteristic muscle MRI pattern.

Adult↗

PubMed1989

Induced frameshifting mechanism of replication for an information-carrying scrapie prion.

A specific mistranslation mechanism for the replication of an infectious protein is described. The feedback mechanism requires the infectious agent to induce concerted frameshifts during the translation of a cellular gene. Each module of the tandem repeat region of the gene encoding the prion protein (PrP) associated with scrapie infectivity contains multiple sites of potential ribosomal frameshifting. It is proposed that some aberrant variants of PrP containing frameshifted peptides within the octapeptide repeat region of the protein backbone are able to replicate and cause scrapie by interfering with the translation and simultaneous translocation of nascent PrP molecules into the lumen of the endoplasmic reticulum. The model provides a plausible explanation for the behaviour of host-adapted scrapie strains as well as the aetiology of scrapie-like diseases. The hypothesis that a mistranslated PrP is the scrapie agent can also explain discrepancies between the published amino acid sequence of PrP and the sequence deduced from the gene.

Amino Acid Sequence↗

PubMed2005

Tandem repeat copy-number variation in protein-coding regions of human genes.

BACKGROUND: Tandem repeat variation in protein-coding regions will alter protein length and may introduce frameshifts. Tandem repeat variants are associated with variation in pathogenicity in bacteria and with human disease. We characterized tandem repeat polymorphism in human proteins, using the UniGene database, and tested whether these were associated with host defense roles. RESULTS: Protein-coding tandem repeat copy-number polymorphisms were detected in 249 tandem repeats found in 218 UniGene clusters; observed length differences ranged from 2 to 144 nucleotides, with unit copy lengths ranging from 2 to 57. This corresponded to 1.59% (218/13,749) of proteins investigated carrying detectable polymorphisms in the copy-number of protein-coding tandem repeats. We found no evidence that tandem repeat copy-number polymorphism was significantly elevated in defense-response proteins (p = 0.882). An association with the Gene Ontology term 'protein-binding' remained significant after covariate adjustment and correction for multiple testing. Combining this analysis with previous experimental evaluations of tandem repeat polymorphism, we estimate the approximate mean frequency of tandem repeat polymorphisms in human proteins to be 6%. Because 13.9% of the polymorphisms were not a multiple of three nucleotides, up to 1% of proteins may contain frameshifting tandem repeat polymorphisms. CONCLUSION: Around 1 in 20 human proteins are likely to contain tandem repeat copy-number polymorphisms within coding regions. Such polymorphisms are not more frequent among defense-response proteins; their prevalence among protein-binding proteins may reflect lower selective constraints on their structural modification. The impact of frameshifting and longer copy-number variants on protein function and disease merits further investigation.

Frameshift Mutation↗

PubMed2006

CD14-dependent modulation of NF-kappaB alternative splicing in the lung after burn injury.

Nuclear factor kappa-B (NF-kappaB), a key downstream player of the LPS signaling pathway, has been shown to undergo alternative splicing in in vitro studies. In this study, we examined the effect of injury and the role of CD14 on NF-kappaB alternative splicing using a murine burn model. CD14 knockout and respective wild-type mice were sacrificed after 18% total body surface area burn. RT-PCR and subsequent sequencing analysis revealed that injury induced multiple novel splicing variants of relA, relB, and NF-kappaB2 in the lungs of CD14 knockout but not wild-type mice. These novel variants resulted either from exon skipping, alternative usage of splicing signals, or intron retention. All but one variant resulted in a frameshift leading to premature termination of translation. These splicing variants encoded for proteins that lacked the domains essential for NF-kappaB transcription factor functions. Two NF-kappaB2 variants acquired only minor changes in their C-terminus that might affect their post-translational cleavage into active isoforms. These results suggest that alternative splicing may be one of the mechanisms by which NF-kappaB activity in the lungs can be regulated after injury. Furthermore, the CD14-mediated LPS signaling pathway may play a role in the regulation of NF-kappaB alternative splicing in the lungs after injury.

Alternative Splicing↗