Functional Analyses of c.2268dup in Thyroid Peroxidase Gene Associated with Goitrous Congenital Hypothyroidism
Joint Authors
Ng, Khoon Leong
Lee, Ching Chin
Mat Junit, Sarni
Lim, Chor Yin
Harun, Fatimah
Jalaludin, Muhammad Yazid
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-03-17
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
The c.2268dup mutation in thyroid peroxidase (TPO) gene was reported to be a founder mutation in Taiwanese patients with dyshormonogenetic congenital hypothyroidism (CH).
The functional impact of the mutation is not well documented.
In this study, homozygous c.2268dup mutation was detected in two Malaysian-Chinese sisters with goitrous CH.
Normal and alternatively spliced TPO mRNA transcripts were present in thyroid tissues of the two sisters.
The abnormal transcript contained 34 nucleotides originating from intron 12.
The c.2268dup is predicted to generate a premature termination codon (PTC) at position 757 (p.Glu757X).
Instead of restoring the normal reading frame, the alternatively spliced transcript has led to another stop codon at position 740 (p.Asp739ValfsX740).
The two PTCs are located at 116 and 201 nucleotides upstream of the exons 13/14 junction fulfilling the requirement for a nonsense-mediated mRNA decay (NMD).
Quantitative RT-PCR revealed an abundance of unidentified transcripts believed to be associated with the NMD.
TPO enzyme activity was not detected in both patients, even though a faint TPO band of about 80 kD was present.
In conclusion, the c.2268dup mutation leads to the formation of normal and alternatively spliced TPO mRNA transcripts with a consequential loss of TPO enzymatic activity in Malaysian-Chinese patients with goitrous CH.
American Psychological Association (APA)
Lee, Ching Chin& Harun, Fatimah& Jalaludin, Muhammad Yazid& Lim, Chor Yin& Ng, Khoon Leong& Mat Junit, Sarni. 2014. Functional Analyses of c.2268dup in Thyroid Peroxidase Gene Associated with Goitrous Congenital Hypothyroidism. BioMed Research International،Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-466665
Modern Language Association (MLA)
Lee, Ching Chin…[et al.]. Functional Analyses of c.2268dup in Thyroid Peroxidase Gene Associated with Goitrous Congenital Hypothyroidism. BioMed Research International No. 2014 (2014), pp.1-11.
https://search.emarefa.net/detail/BIM-466665
American Medical Association (AMA)
Lee, Ching Chin& Harun, Fatimah& Jalaludin, Muhammad Yazid& Lim, Chor Yin& Ng, Khoon Leong& Mat Junit, Sarni. Functional Analyses of c.2268dup in Thyroid Peroxidase Gene Associated with Goitrous Congenital Hypothyroidism. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-466665
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-466665