Two pathogenic mutations located within the 5'-regulatory sequence of the GJB1 gene affecting initiation of transcription and translation

• Authors: Dagmara Kabzińska , Katarzyna Kotruchow , Barbara Ryniewicz , Andrzej Kochański
• Languages of publication: EN

Abstracts

EN

In contrast to mutations in the coding sequences of a genes involved in the pathogenesis of Charcot-Marie-Tooth disease (CMT), little is known about CMT phenotypes resulting from a DNA variants located in regulatory sequences of a given " CMT gene". Charcot-Marie-Tooth type X1 disease (CMTX1) is caused by mutations in the GJB1 gene coding for an ion channel known as connexin, with a molecular mass of 32 kDa (Cx32). Only 0.01% of the GJB1 gene mutations have been reported in its 5' regulatory sequence. Pathogenic mutations occured in the internal ribosome entry site (IRES) are extremely rarely reported in human genetic disorders. To the best of our knowledge, in this study we report for the first time in an Eastern European population, two CMTX1 families in which two pathogenic mutations in the 5' regulatory sequence of the GJB1 gene (c.-529T>C and -459C>T) have been found. The two mutations identified in our study disturb the 5' UTR sequence in two different ways, by affecting the transcription factor SOX10 binding site (c.-529T>C) and by the disrupting IRES element of GJB1 gene (c.-459C>T). These regions are responsible for transcription (SOX10) and initiation of translation (IRES), respectively. On the basis of our findings that, in contrast to the most DNA sequence variants reported in untranslated regulatory regions of genes, the c.-459C>T and c.-529T>C mutations remain pathogenic in the context of different ethnic background.

Keywords

EN

IRES element; transcription; GJB1 gene; translation; mutations in regulatory elements

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2011
• Volume: 58
• Issue: 3
• Pages: 359-363

Dates

published

2011

received

2011-03-04

revised

2011-04-06

accepted

2011-09-12

(unknown)

2011-09-14

Contributors

author

Dagmara Kabzińska

• Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland

author

Katarzyna Kotruchow

• Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland

author

Barbara Ryniewicz

• Department of Neurology, Medical University of Warszawa, Warsaw, Poland

author

Andrzej Kochański

• Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland

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