scholarly journals A novel de novo COL6A1 mutation emphasizes the role of intron 14 donor splice site defects as a cause of moderate-progressive form of ColVI myopathy – a case report and review of the genotype–phenotype correlation

2017 ◽  
Vol 3 ◽  
pp. 214-220 ◽  
Author(s):  
Agnieszka A. Koppolu ◽  
Agnieszka Madej-Pilarczyk ◽  
Małgorzata Rydzanicz ◽  
Joanna Kosińska ◽  
Piotr Gasperowicz ◽  
...  
Keyword(s):  
Case Report ◽  
Splice Site ◽  
De Novo ◽  
Donor Splice Site ◽  
Phenotype Correlation ◽  
Donor Splice ◽  
Genotype Phenotype Correlation ◽  
Progressive Form

scholarly journals A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Arthur Jacob ◽  
Jennifer Pasquier ◽  
Raphael Carapito ◽  
Frédéric Auradé ◽  
Anne Molitor ◽  
...  
Keyword(s):  
Splice Site ◽  
De Novo ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Genetic Alterations ◽  
Donor Splice Site ◽  
Donor Splice ◽  
First Case ◽  
Synonymous Variant ◽  
Mandibulofacial Dysostosis

Abstract Background Mandibulofacial dysostosis with microcephaly (MFDM) is a rare autosomal dominant genetic disease characterized by intellectual and growth retardations, as well as major microcephaly, induced by missense and splice site variants or microdeletions in the EFTUD2 gene. Case presentation Here, we investigate the case of a young girl with symptoms of MFDM and a normal karyotype. Whole-exome sequencing of the family was performed to identify genetic alterations responsible for this phenotype. We identified a de novo synonymous variant in the EFTUD2 gene. We demonstrated that this synonymous variant disrupts the donor splice-site in intron 9 resulting in the skipping of exon 9 and a frameshift that leads to a premature stop codon. Conclusions We present the first case of MFDM caused by a synonymous variant disrupting the donor splice site, leading to exon skipping.

Severe Homozygous Protein C Deficiency: Identification of a Splice Site Missense Mutation (184, Q → H) in Exon 7 of the Protein C Gene

1994 ◽  
Vol 72 (01) ◽  
pp. 065-069 ◽  
Author(s):  
J M Soria ◽  
D Brito ◽  
J Barceló ◽  
J Fontcuberta ◽  
L Botero ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Gene Product ◽  
Splice Site ◽  
Protein C ◽  
Purpura Fulminans ◽  
Single Strand Conformation Polymorphism ◽  
Donor Splice Site ◽  
Protein C Deficiency ◽  
Donor Splice ◽  
Newborn Child

SummarySingle strand conformation polymorphism (SSCP) analysis of exon 7 of the protein C gene has identified a novel splice site missense mutation (184, Q → H), in a newborn child with purpura fulminans and undetectable protein C levels. The mutation, seen in the homozygous state in the child and in the heterozygous state in her mother, was characterized and found to be a G to C nucleotide substitution at the -1 position of the donor splice site of intron 7 of the protein C gene, which changes histidine 184 for glutamine (184, Q → H). According to analysis of the normal and mutated sequences, this mutation should also abolish the function of the donor splice site of intron 7 of the protein C gene. Since such a mutation is compatible with the absence of gene product in plasma and since DNA sequencing of all protein C gene exons in this patient did not reveal any other mutation, we postulate that mutation 184, Q → H results in the absence of protein C gene product in plasma, which could be the cause of the severe phenotype observed in this patient.

Construction of a helper cell line for avian reticuloendotheliosis virus cloning vectors

1983 ◽  
Vol 3 (12) ◽  
pp. 2241-2249
Author(s):  
S Watanabe ◽  
H M Temin
Keyword(s):  
Cell Line ◽  
Thymidine Kinase ◽  
Splice Site ◽  
Virus Production ◽  
Helper Virus ◽  
Donor Splice Site ◽  
Reticuloendotheliosis Virus ◽  
Donor Splice ◽  
Proviral Dna ◽  
Viral Dnas

We wished to construct cell lines that supply the gene products of gag, pol, and env for the growth of replication-defective reticuloendotheliosis retrovirus vectors without production of the helper virus. To do this, first we located by S1 mapping the donor and acceptor splice sites of reticuloendotheliosis virus strain A. The donor splice site is ca. 850 base pairs from the 5' end of proviral DNA. It is close to or overlaps the encapsidation sequences for viral RNA. The splice acceptor site is ca. 5.6 kilobase pairs from the 5' end of proviral DNA. Therefore, the encapsidation sequences and the donor splice site were removed from viral DNA to give expression of the gag and pol genes without virus production. The promoter in the long terminal repeat was fused to a site near the first ATG codon of the env gene, thereby deleting the encapsidation sequences and the gag and pol genes to give expression of the env gene without virus production. The permissive canine cell line D17 was transfected with the two modified viral DNAs. Two cell clones that contain both modified viral DNAs support the production of replication-defective spleen necrosis virus-thymidine kinase recombinant retrovirus vectors without the production of helper virus. To prevent recombination, the vector contains deletions that overlap with deletions in the integrated helper virus DNAs. This helper cell-vector system will be useful to derive infectious recombinant virus stocks of high titer (over 10(5) thymidine kinase transforming units per ml) which are able to infect avian, rat, and dog cells without the aid of helper virus.

Role of genotype–phenotype correlation in prognostication of a child with a novel potassium channelopathy

2022 ◽  
Vol 0 (0) ◽  
pp. 0
Author(s):  
Lokesh Saini ◽  
Bhanudeep Singanamalla ◽  
Ramesh Natarajan ◽  
Priyanka Madaan
Keyword(s):  
Phenotype Correlation ◽  
Genotype Phenotype Correlation

Molecular Mechanisms of FVII Deficiency: Expression of Mutations Clustered in the IVS7 Donor Splice Site of Factor VII Gene

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1646-1651 ◽  
Author(s):  
M. Pinotti ◽  
R. Toso ◽  
R. Redaelli ◽  
M. Berrettini ◽  
G. Marchetti ◽  
...  
Keyword(s):  
Splice Site ◽  
Molecular Mechanisms ◽  
Catalytic Domain ◽  
Point Mutations ◽  
Factor Vii ◽  
Donor Splice Site ◽  
Donor Splice ◽  
Expression Studies ◽  
Fvii Deficiency ◽  
American Society

Abstract In three Italian patients, two point mutations and a short deletion were found in the intron 7 of factor VII gene, clustered in the donor splice site and located in the first of several repeats. The mutation 9726+5G→A, the most frequent cause of symptomatic factor VII deficiency in Italy, as well as the deletion (9729del4) gave rise in expression studies to abnormally spliced transcripts, which were exclusively produced from the cryptic site in the second repeat. The insertion in the mature mRNA of the first intronic repeat caused (9726+5G→A) a reading frameshift, abolishing most of the factor VII catalytic domain, or produced (9729del4), an altered factor with 11 additional residues, the activity of which was not detectable in the cell medium after mutagenesis and expression studies. Studies of factor VII ectopic mRNA from leukocytes and expression studies indicated that the deleted gene produced 30% of normally spliced transcript. Differently, the 9726+5G→A mutation permitted a very low level (0.2% to 1%) of correct splicing to occur, which could be of great importance to prevent the onset, in the homozygous patients, of most of the life-threatening bleeding symptoms. The 9726+7A→G mutation was found to be a rare and functionally silent polymorphism. These findings, which provide further evidence of the interplay of sequence and position in the 5′ splice site selection, throw light on the heterogeneous molecular bases and clinical phenotypes of FVII deficiency. © 1998 by The American Society of Hematology.

scholarly journals Genotype–phenotype correlation of LMNA variants involving the Arg541 residue: a case report with multimodality imaging and literature review

2020 ◽  
Vol 7 (5) ◽  
pp. 3169-3173
Author(s):  
Andrea Di Marco ◽  
María Ruiz‐Cueto ◽  
Joel Salazar‐Mendiguchía ◽  
Eduard Claver ◽  
Gerard Roura ◽  
...  
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Multimodality Imaging ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation

scholarly journals GEN-03 GENOTYPE-PHENOTYPE CORRELATION IN 111 FAMILIES OF VON HIPPEL-LINDAU DISEASE IN JAPAN

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii8-ii8
Author(s):  
Hiroshi Kanno ◽  
Tetsuya Yoshizumi ◽  
Masamichi Shinonaga ◽  
Masahiro Yao
Keyword(s):  
Amino Acids ◽  
Missense Mutation ◽  
Splice Site ◽  
Phenotype Correlation ◽  
Exon 2 ◽  
Endolymphatic Sac Tumor ◽  
Von Hippel Lindau ◽  
Genotype Phenotype Correlation ◽  
Exon 1 ◽  
Vhl Disease

Abstract BACKGROUND AND AIM von Hippel-Lindau (VHL) disease is a hereditary disease which manifest central nervous system (CNS) hemangioblastoma, retinal angioma, renal cell carcinoma (RCC), pheochromocytoma, endolymphatic sac tumor, and pancreas cyst. The VHL gene is located at 3p25.3 and is corresponding to 213 amino acids. Genotype-phenotype correlation analyses of VHL disease have been recently reported from several foreign countries, but the genotype-phenotype correlation has not been characterized since above 10 years ago. Therefore, this study aimed to evaluate the VHL mutation spectrum and genotype-phenotype correlations in Japanese VHL patients. METHODS Blood samples of 111 unrelated families of VHL disease were collected and DNAs were extracted. Direct sequencing and real-time PCR analysis were performed. Consequently, the clinical manifestations and family histories of the subjects were evaluated. RESULTS We identified VHL mutations as follows: missense 47; deletion 17; insertion 5; nonsense 8; splice-site 9; larger deletion 25. At hot-spot codon 167, 4 minsense mutations were identified, with Arg167Trp, 4 cases; Arg167Gln2, 2 cases. At codon 155, splice-site mutations were identified at 6 cases. Mutation sites were distributed in exon 1, 45; exon 2, 21; exon 3, 36. Large deletions were distributed in exon 1 & 2, 1; exon 2& 3, 1; all exons, 11. Genotype-phenotype correlation analysis revealed that age-specific risk and number of CNS hemangioblastoma were significantly higher in subjects carrying missense mutation within HIF-α binding site or non-missense mutation (P < 0.05). In addition, penetrance of RCC was significantly higher in subjects carrying non-missense mutation (P < 0.05). CONCLUSIONS The results of this study were similar to the previous foreign studies. This study provides insight into the genotype-phenotype correlation in that amino acids substitutions in the HIF- α binding and non-sense mutations may predispose VHL patients to age-related risk and number of CNS hemangioblastoma.

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