Expanded clinical and genetic characterization of autosomal recessive HMGCR-related muscular dystrophy

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

Institutions

Publication Details

Journal
Journal of Neuromuscular Diseases
Published
2026-03-29
DOI
https://doi.org/10.1177/22143602261436296
Primary Topic
Muscle Physiology and Disorders
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Expanded clinical and genetic characterization of autosomal recessive HMGCR-related muscular dystrophy

Sahar Sedighzadeh, Ayça Dilruba Aslanger, Mahdiyeh Behnam, André Mégarbané et al.
Journal of Neuromuscular Diseases
Muscle Physiology and Disorders
article

Expanded clinical and genetic characterization of autosomal recessive HMGCR-related muscular dystrophy

Sahar Sedighzadeh, Ayça Dilruba Aslanger, Mahdiyeh Behnam, André Mégarbané, Sandra Sabbagh, Yavuz Oktay, Asuman Gedikbaşı, Cybel Mehawej, Sami Bizzari, Sandra Corbani, Meisam Sharifzadeh, Mohammad Shahrooei, Pratibha Nair, Javad Mohammadi-Asl, İpek Polat, Sinan Akbaş, Aboulfazl Rad, Gabriela Oprea, Murtadha Ali, Stephany El-Hayek, Pejman Rohani, Eliane Chouery, Henry Houlden, Uluç Yiş, Gozde Yesil, Reza Maroofian, Volkan Karaman, J Andoni Urtizberea
article en

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.

Journal of Neuromuscular Diseases
Dokuz Eylül University (TR), Shahid Chamran University of Ahvaz (IR), Rega Institute for Medical Research (BE), Mohammed Bin Rashid University of Medicine and Health Sciences (AE), Children's Medical Center (IR), Institut de Myologie (FR), Fondation Jérôme-Lejeune (FR), National Hospital for Neurology and Neurosurgery (GB), Hôtel-Dieu de France (LB), Semnan University of Medical Sciences (IR), Genetic Technologies (Australia) (AU), University College London (GB), University of Rostock (DE), Lebanese American University (LB), Istanbul University (TR), Tehran University of Medical Sciences (IR), KU Leuven (BE)
Good health and well-being
Openalex Percentile: Top 4%
Muscle Physiology and Disorders
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.