Homozygous nonsense mutation in SGCA is a common cause of limb-girdle muscular dystrophy in Assiut, Egypt

Hemakumar M. Reddy; Sherifa A. Hamed; Monkol Lek; Satomi Mitsuhashi; Elicia Estrella; Michael D. Jones; Lane J. Mahoney; Anna R. Duncan; Kyung ah Cho; Daniel G. Macarthur; Louis M. Kunkel; Peter B. Kang

doi:10.1002/mus.25094

Homozygous nonsense mutation in SGCA is a common cause of limb-girdle muscular dystrophy in Assiut, Egypt

Hemakumar M. Reddy, Sherifa A. Hamed, Monkol Lek, Satomi Mitsuhashi, Elicia Estrella, Michael D. Jones, Lane J. Mahoney, Anna R. Duncan, Kyung ah Cho, Daniel G. Macarthur, Louis M. Kunkel, Peter B. Kang

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Introduction: The genetic causes of limb-girdle muscular dystrophy (LGMD) have been studied in numerous countries, but such investigations have been limited in Egypt. Methods: A cohort of 30 families with suspected LGMD from Assiut, Egypt, was studied using immunohistochemistry, homozygosity mapping, Sanger sequencing, and whole exome sequencing. Results: Six families were confirmed to have pathogenic mutations, 4 in SGCA and 2 in DMD. Of these, 3 families harbored a single nonsense mutation in SGCA, suggesting that this may be a common mutation in Assiut, Egypt, originating from a founder effect. Conclusions: The Assiut region in Egypt appears to share at least several of the common LGMD genes found in other parts of the world. It is notable that 4 of the 6 mutations were ascertained by means of whole exome sequencing, even though it was the last approach adopted. This illustrates the power of this technique for identifying causative mutations for muscular dystrophies. Muscle Nerve 54: 690–695, 2016.

Original language	English (US)
Pages (from-to)	690-695
Number of pages	6
Journal	Muscle and Nerve
Volume	54
Issue number	4
DOIs	https://doi.org/10.1002/mus.25094
State	Published - Oct 1 2016
Externally published	Yes

Bibliographical note

Funding Information:
The authors thank the participants for enrolling in the study, along with Marielle Thorne for assistance with sample processing. This project was funded by NIH R01 NS080929 (H.M.R. and P.B.K.), R01 GM104371 (D.G.M.), Muscular Dystrophy Association Grant 186796 (P.B.K.), the Bernard F. and Alva B. Gimbel Foundation (L.M.K.), and the Department of Pediatrics at the University of Florida College of Medicine (H.M.R., M.D.J., K.A.C., and P.B.K.). Sanger DNA sequencing was performed at the IDDRC Molecular Genetics Core Facility at Boston Children's Hospital and the Interdisciplinary Center for Biotechnology Research (ICBR) Sanger Sequencing Core at the University of Florida. Exome sequencing was supported by Medical Sequencing Program Grant U54HG003067 from the National Human Genome Research Institute.

Publisher Copyright:
© 2016 Wiley Periodicals, Inc.

Keywords

founder effect
homozygosity mapping
limb-girdle muscular dystrophy
sarcoglycanopathy
whole exome sequencing

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Homozygous nonsense mutation in SGCA is a common cause of limb-girdle muscular dystrophy in Assiut, Egypt",

abstract = "Introduction: The genetic causes of limb-girdle muscular dystrophy (LGMD) have been studied in numerous countries, but such investigations have been limited in Egypt. Methods: A cohort of 30 families with suspected LGMD from Assiut, Egypt, was studied using immunohistochemistry, homozygosity mapping, Sanger sequencing, and whole exome sequencing. Results: Six families were confirmed to have pathogenic mutations, 4 in SGCA and 2 in DMD. Of these, 3 families harbored a single nonsense mutation in SGCA, suggesting that this may be a common mutation in Assiut, Egypt, originating from a founder effect. Conclusions: The Assiut region in Egypt appears to share at least several of the common LGMD genes found in other parts of the world. It is notable that 4 of the 6 mutations were ascertained by means of whole exome sequencing, even though it was the last approach adopted. This illustrates the power of this technique for identifying causative mutations for muscular dystrophies. Muscle Nerve 54: 690–695, 2016.",

keywords = "founder effect, homozygosity mapping, limb-girdle muscular dystrophy, sarcoglycanopathy, whole exome sequencing",

author = "Reddy, {Hemakumar M.} and Hamed, {Sherifa A.} and Monkol Lek and Satomi Mitsuhashi and Elicia Estrella and Jones, {Michael D.} and Mahoney, {Lane J.} and Duncan, {Anna R.} and Cho, {Kyung ah} and Macarthur, {Daniel G.} and Kunkel, {Louis M.} and Kang, {Peter B.}",

note = "Funding Information: The authors thank the participants for enrolling in the study, along with Marielle Thorne for assistance with sample processing. This project was funded by NIH R01 NS080929 (H.M.R. and P.B.K.), R01 GM104371 (D.G.M.), Muscular Dystrophy Association Grant 186796 (P.B.K.), the Bernard F. and Alva B. Gimbel Foundation (L.M.K.), and the Department of Pediatrics at the University of Florida College of Medicine (H.M.R., M.D.J., K.A.C., and P.B.K.). Sanger DNA sequencing was performed at the IDDRC Molecular Genetics Core Facility at Boston Children's Hospital and the Interdisciplinary Center for Biotechnology Research (ICBR) Sanger Sequencing Core at the University of Florida. Exome sequencing was supported by Medical Sequencing Program Grant U54HG003067 from the National Human Genome Research Institute. Publisher Copyright: {\textcopyright} 2016 Wiley Periodicals, Inc.",

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doi = "10.1002/mus.25094",

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T1 - Homozygous nonsense mutation in SGCA is a common cause of limb-girdle muscular dystrophy in Assiut, Egypt

AU - Reddy, Hemakumar M.

AU - Hamed, Sherifa A.

AU - Lek, Monkol

AU - Mitsuhashi, Satomi

AU - Estrella, Elicia

AU - Jones, Michael D.

AU - Mahoney, Lane J.

AU - Duncan, Anna R.

AU - Cho, Kyung ah

AU - Macarthur, Daniel G.

AU - Kunkel, Louis M.

AU - Kang, Peter B.

N1 - Funding Information: The authors thank the participants for enrolling in the study, along with Marielle Thorne for assistance with sample processing. This project was funded by NIH R01 NS080929 (H.M.R. and P.B.K.), R01 GM104371 (D.G.M.), Muscular Dystrophy Association Grant 186796 (P.B.K.), the Bernard F. and Alva B. Gimbel Foundation (L.M.K.), and the Department of Pediatrics at the University of Florida College of Medicine (H.M.R., M.D.J., K.A.C., and P.B.K.). Sanger DNA sequencing was performed at the IDDRC Molecular Genetics Core Facility at Boston Children's Hospital and the Interdisciplinary Center for Biotechnology Research (ICBR) Sanger Sequencing Core at the University of Florida. Exome sequencing was supported by Medical Sequencing Program Grant U54HG003067 from the National Human Genome Research Institute. Publisher Copyright: © 2016 Wiley Periodicals, Inc.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Introduction: The genetic causes of limb-girdle muscular dystrophy (LGMD) have been studied in numerous countries, but such investigations have been limited in Egypt. Methods: A cohort of 30 families with suspected LGMD from Assiut, Egypt, was studied using immunohistochemistry, homozygosity mapping, Sanger sequencing, and whole exome sequencing. Results: Six families were confirmed to have pathogenic mutations, 4 in SGCA and 2 in DMD. Of these, 3 families harbored a single nonsense mutation in SGCA, suggesting that this may be a common mutation in Assiut, Egypt, originating from a founder effect. Conclusions: The Assiut region in Egypt appears to share at least several of the common LGMD genes found in other parts of the world. It is notable that 4 of the 6 mutations were ascertained by means of whole exome sequencing, even though it was the last approach adopted. This illustrates the power of this technique for identifying causative mutations for muscular dystrophies. Muscle Nerve 54: 690–695, 2016.

AB - Introduction: The genetic causes of limb-girdle muscular dystrophy (LGMD) have been studied in numerous countries, but such investigations have been limited in Egypt. Methods: A cohort of 30 families with suspected LGMD from Assiut, Egypt, was studied using immunohistochemistry, homozygosity mapping, Sanger sequencing, and whole exome sequencing. Results: Six families were confirmed to have pathogenic mutations, 4 in SGCA and 2 in DMD. Of these, 3 families harbored a single nonsense mutation in SGCA, suggesting that this may be a common mutation in Assiut, Egypt, originating from a founder effect. Conclusions: The Assiut region in Egypt appears to share at least several of the common LGMD genes found in other parts of the world. It is notable that 4 of the 6 mutations were ascertained by means of whole exome sequencing, even though it was the last approach adopted. This illustrates the power of this technique for identifying causative mutations for muscular dystrophies. Muscle Nerve 54: 690–695, 2016.

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KW - sarcoglycanopathy

KW - whole exome sequencing

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Homozygous nonsense mutation in SGCA is a common cause of limb-girdle muscular dystrophy in Assiut, Egypt

Abstract

Bibliographical note

Keywords

UN SDGs

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