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Whole-exome sequencing identified compound heterozygous variants in the TTN gene causing Salih myopathy with dilated cardiomyopathy in an Iranian family

Part of: Basic Science

Published online by Cambridge University Press:  16 November 2021

Mohammad Mahdavi ,
Neda Mohsen-Pour ,
Majid Maleki ,
Mahshid Hesami ,
Niloofar Naderi ,
Golnaz Houshmand ,
Hamid R. Rasouli Jazi ,
Hossein Shahzadi  and
Samira Kalayinia Open the ORCID record for Samira Kalayinia [Opens in a new window]
Mohammad Mahdavi
Affiliation:
Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Neda Mohsen-Pour
Affiliation:
Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
Majid Maleki
Affiliation:
Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Mahshid Hesami
Affiliation:
Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Niloofar Naderi
Affiliation:
Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Golnaz Houshmand
Affiliation:
Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Hamid R. Rasouli Jazi
Affiliation:
Biotechnology Research Center, Malek Ashtar University of Technology, Tehran, Iran
Hossein Shahzadi
Affiliation:
Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Samira Kalayinia*
Affiliation:
Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
*
Author for correspondence: S. Kalayinia, PhD, Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran. Tel: +98 (21) 23923148; Fax: +98 (21) 22663213. E-mail: [email protected]
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Abstract

Background:

Salih myopathy, characterised by both congenital myopathy and fatal dilated cardiomyopathy, is an inherited muscle disorder that affects skeletal and cardiac muscles. TTN has been identified as the main cause of this myopathy, the enormous size of this gene poses a formidable challenge to molecular genetic diagnostics.

Method:

In the present study, whole-exome sequencing, cardiac MRI, and metabolic parameter assessment were performed to investigate the genetic causes of Salih myopathy in a consanguineous Iranian family who presented with titinopathy involving both skeletal and heart muscles in an autosomal recessive inheritance pattern.

Results:

Two missense variants of TTN gene (NM_001267550.2), namely c.61280A>C (p. Gln20427Pro) and c.54970G>A (p. Gly18324Ser), were detected and segregations were confirmed by polymerase chain reaction-based Sanger sequencing.

Conclusions:

The compound heterozygous variants, c.61280A>C, (p. Gln20427Pro) and c.54970G>A, (p. Gly18324Ser) in the TTN gene appear to be the cause of Salih myopathy and dilated cardiomyopathy in the family presented. Whole-exome sequencing is an effective molecular diagnostic tool to identify the causative genetic variants of large genes such as TTN.

Keywords

Dilated cardiomyopathySalih myopathytitinopathyTTNwhole-exome sequencingcompound heterozygous
Type
Original Article
Information
Cardiology in the Young , Volume 32 , Issue 9 , September 2022 , pp. 1462 - 1467
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Copyright
© The Author(s), 2021. Published by Cambridge University Press

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Footnotes

Mohammad Mahdavi and Neda Mohsen-Pour are contributed equally to this work.

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