Tehran University of Medical Sciences

Science Communicator Platform

Share By
Expanded Clinical and Genetic Characterization of Autosomal Recessive Hmgcr-Related Muscular Dystrophy Publisher Pubmed



El Hayek S ; Rad A ; Sedighzadeh S ; Yesil G ; Sabbagh S ; Shahrooei M ; Nair P ; Gedikbasi A ; Bizzari S ; Ali M ; Chouery E ; Mehawej C ; Aslanger A ; Rohani P Show All Authors
Authors
  1. El Hayek S
  2. Rad A
  3. Sedighzadeh S
  4. Yesil G
  5. Sabbagh S
  6. Shahrooei M
  7. Nair P
  8. Gedikbasi A
  9. Bizzari S
  10. Ali M
  11. Chouery E
  12. Mehawej C
  13. Aslanger A
  14. Rohani P
  15. Sharifzadeh M
  16. Akbas S
  17. Mohammadi Asl J
  18. Behnam M
  19. Corbani S
  20. Karaman V
  21. Yis U
  22. Oktay Y
  23. Polat I
  24. Urtizberea J A
  25. Houlden H
  26. Maroofian R
  27. Oprea G
  28. Megarbane A

Source: Journal of Neuromuscular Diseases Published:2026


Abstract

Autosomal recessive Limb-Girdle Muscular Dystrophy type R28 (LGMDR28; OMIM #620375) is one of the most recently identified subtypes of recessive LGMD. To date, 17 affected individuals from eight unrelated families have been reported to harbor biallelic variants in the HMGCR gene. Here, we report eleven individuals from six unrelated Middle Eastern families diagnosed with LGMDR28 and carrying homozygous variants in HMGCR. Our cohort recapitulated most of the previously described clinical features of the HMGCR-related phenotype. In addition, we also report a family with congenital onset of the condition as well as two affected individuals with liver failure. Through genome and exome sequencing, we identified three novel homozygous missense variants; c.2519G->A, p.(Arg840Gln), c.1784G->A, p.(Arg595His), and c.1783C>T, p.(Arg595Cys) and a homozygous in-frame deletion (c.1522_1524del, p.(Ser508del)) previously reported in compound heterozygous state with a second relevant variant and very recently as homozygous in an unrelated proband. This study consolidates the pathogenic role of HMGCR in LGMDR28 while expanding the phenotypic and mutations spectrum of LGMDR28. © The Author(s) 2026. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
Related Docs
View other Related Docs
1. Identification of a Novel Missense C.386G > a Variant in a Boy With the Pomgnt1-Related Muscular Dystrophy-Dystroglycanopathy, Acta Neurologica Belgica (2021)
2. Sequential Targeted Exome Sequencing of 1001 Patients Affected by Unexplained Limb-Girdle Weakness, Genetics in Medicine (2020)
3. Novel Genotypes, Phenotypes, and Triggers in Humans With Otulin Haploinsufficiency, Journal of Human Immunity (2025)
Experts (# of related papers)
View all Related Experts
Mahmoudreza Ashrafi (2)
Ali Reza Tavasoli (2)
Other Related Docs
4. Homozygosity Mapping and Direct Sequencing Identify a Novel Pathogenic Variant in the Cisd2 Gene in an Iranian Wolfram Syndrome Family, Acta Diabetologica (2020)
5. Expanding Phenotype Heterogeneity of Nars2 by Presenting Subdural Hematoma and Parenchymal Hemorrhage, Journal of Clinical Laboratory Analysis (2023)
6. A Novel Pathogenic Variant in the Lrtomt Gene Causes Autosomal Recessive Non-Syndromic Hearing Loss in an Iranian Family, BMC Medical Genetics (2020)
7. Primary and Secondary Microcephaly, Global Developmental Delay, and Seizure in Two Siblings Caused by a Novel Missense Variant in the Znf335 Gene, Journal of Molecular Neuroscience (2022)
8. A Novel Pathogenic Variant in the Fzd6 Gene Causes Recessive Nail Dysplasia in a Large Iranian Kindred, Journal of Dermatological Science (2017)