Two novel mutations in the thyroglobulin gene as cause of congenital hypothyroidism: Identification a cryptic donor splice site in the exon 19

2012 ◽  
Vol 348 (1) ◽  
pp. 313-321 ◽  
Author(s):  
Héctor M. Targovnik ◽  
Thomas Edouard ◽  
Viviana Varela ◽  
Maithé Tauber ◽  
Cintia E. Citterio ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Splice Site ◽  
Donor Splice Site ◽  
Novel Mutations ◽  
Donor Splice ◽  
Thyroglobulin Gene ◽  
Exon 19

scholarly journals Two Novel Mutations in the Serpina7 Gene Are Associated with Complete Deficiency of Thyroxine-Binding Globulin

2015 ◽  
Vol 4 (Suppl. 1) ◽  
pp. 108-112 ◽  
Author(s):  
Lars C. Moeller ◽  
Yaw Appiagyei-Dankah ◽  
Birgit Köhler ◽  
Heike Biebermann ◽  
Onno E. Janssen ◽  
...  
Keyword(s):  
Splice Site ◽  
Donor Splice Site ◽  
Coding Region ◽  
Novel Mutations ◽  
Single Nucleotide ◽  
Thyroxine Binding Globulin ◽  
Direct Dna Sequencing ◽  
Donor Splice ◽  
Intron 1

Background: Thyroxine-binding globulin (TBG) is the main transport protein for T4 in blood. Until now, 22 mutations leading to complete TBG deficiency (TBG-CD) have been reported. Objective: We report two mutations associated with TBG-CD found in patients from Andrews, S.C., USA (TBG-CD-Andrews), and Berlin, Germany (TBG-CD-Berlin). Methods: Automated chemiluminescence immunoassays were used for the determination of TSH, free and total T4 and T3 (fT4, TT4, TT3) and TBG. Direct DNA sequencing was used to identify the TBG mutations in the propositi. Results: TBG-CD-Andrews was found in a 1-month-old boy who was euthyroid with normal TSH and fT4, but reduced TT4, indicating TBG deficiency. TBG was not detectable, confirming TBG-CD. No mutation in the coding region and the promoter of the TBG gene was found, but a single nucleotide substitution in intron 1 disrupts the donor splice site of exon 0 (IVS1+2T>C). Another mutation was found in an 11-year-old boy. He was also euthyroid with normal fT4 and TSH. However, TT4 and TT3 were low, suggesting TBG-CD. Sequencing revealed a 79-nucleotide deletion, ranging from intron 3 into exon 3. Conclusion: We report two novel mutations of the TBG gene associated with TBG-CD. Whereas most TBG-CDs are caused by small deletions, in TBG-CD-Andrews the disruption of a donor splice site was detected, whilst in TBG-CD-Berlin the largest deletion in the Serpina7 gene to date was found.

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.

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.

A Further case of β-Thalassemia with an Homozygous T→C Substitution at the Donor Splice Site of the First Intervening Sequence of the β-Globin Gene

Hemoglobin ◽  
1989 ◽  
Vol 13 (6) ◽  
pp. 619-621 ◽  
Author(s):  
A. M. Lossi ◽  
M. Milland ◽  
J. L. Bergé-Lefranc ◽  
D. Lena-Russo ◽  
H. Perrimond
Keyword(s):  
Splice Site ◽  
Globin Gene ◽  
Donor Splice Site ◽  
Donor Splice

A mutation (IVS8+0.6kbdelTC) creating a new donor splice site activates a cryptic exon in an

1998 ◽  
Vol 103 (6) ◽  
pp. 686 ◽  
Author(s):  
R. Vervoort ◽  
Richard Gitzelmann ◽  
W. Lissens ◽  
Inge Liebaers
Keyword(s):  
Splice Site ◽  
Donor Splice Site ◽  
Cryptic Exon ◽  
Donor Splice
Sign in / Sign up

Export Citation Format

Share Document