Expanded clinical and genetic characterization of autosomal recessive HMGCR-related muscular dystrophy
Year: 2026
Type: article
Study design: Observational Study
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.
Authors: Stephany El-Hayek, Aboulfazl Rad, Sahar Sedighzadeh, Gozde Yesil, Sandra Sabbagh, Mohammad Shahrooei, Pratibha Nair, Asuman Gedikbaşı, Sami Bizzari, Murtadha Ali, Eliane Chouery, Cybel Mehawej, Ayca Aslanger, Pejman Rohani, Meisam Sharifzadeh, Sinan Akbas, Javad Mohammadi-asl, Mahdiyeh Behnam, Sandra Corbani, Volkan Karaman, Uluç Yiş, Yavuz Oktay, Ipek Polat, J Andoni Urtizberea, Henry Houlden, Reza Maroofian, Gabriela Oprea, Andre Megarbane
Institutions: Centre for Arab Genomic Studies, Shahid Chamran University of Ahvaz, Istanbul University, Hôtel-Dieu de France, KU Leuven, Lebanese American University, Tehran University of Medical Sciences, Semnan University of Medical Sciences, Dokuz Eylül University, Izmir Biomedicine and Genome Center, Institut de Myologie, UCL Queen Square Institute of Neurology, Fondation Jérôme-Lejeune
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7142660795