Limb-girdle muscular dystrophy type 2I: two Chinese families and a review in Asian patients

ABSTRACT

Background: Limb-girdle muscular dystrophy type 2I (LGMD2I) is an autosomal recessive hereditary disorder caused by mutations in the fukutin-related protein (FKRP) gene. Although the features of the disorder in European patients have been summarized, Asian patients with LGMD2I have rarely been reported. Thus, the clinical differences in LGMD2I between Asian and European patients and the associated genetic changes remain unclear.

Methods: We reported detailed clinical data as well as results from muscle biopsy, muscle MRI and genetic analysis of the FKRP gene in two unrelated Chinese families with LGMD2I. Additionally, a review of the literature focusing on the clinical and mutational features of LGMD2I in Asian patients was performed.

Results: The muscle biopsy results showed dystrophic features. Immunohistochemical staining revealed decreased glycosylations on α-dystroglycan. The muscle MRI results showed that the gluteus maximus, adductor, biceps femoris, vastus intermedius and vastus lateralis were severely affected. The patients in the two families harbored the same compound heterozygous mutations (c.545A>G and c.948delC). One patient showed significant clinical improvement after corticosteroid treatment.

Conclusion: Our study expanded the reported spectrum of Asian LGMD2I patients. Our literature review revealed that pathogenic mutations in the FKRP gene in Asian LGMD2I patients are compound heterozygous rather than homozygous. Compound heterozygous Asian patients have a mild phenotype but frequently show respiratory and cardiac impairments. Corticosteroids may be beneficial for the treatment of LGMD2I and should be further investigated.

KEYWORDS:

• Limb-girdle muscular dystrophy type 2I
• FKRP gene
• α-dystroglycan
• clinical phenotype
• MRI
• steroid treatment

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (U1505222, Beijing), National key clinical specialty discipline construction program and key clinical specialty discipline construction program of Fujian, P.R.C.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

National Natural Science Foundation of China [grant number U1505222]; National key clinical specialty discipline construction program and key clinical specialty discipline construction program of Fujian, P.R.C.

Notes on contributors

Dan-Ni Wang

Dan-Ni Wang is a doctoral candidate at Department of Neurology and Institute of Neurology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Zhi-Qiang Wang

Zhi-Qiang Wang is a professor at Department of Neurology and Institute of Neurology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China. He also works in Fujian Key Laboratory of Molecular Neurology, Fuzhou, China.

Yu-Qing Chen

Yu-Qing Chen is a teacher at Department of Pathology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.

Guo-Rong Xu

Guo-Rong Xu is a clinical doctor at Department of Neurology and Institute of Neurology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Min-Ting Lin

Min-Ting Lin is a technician at Fujian Key Laboratory of Molecular Neurology, Fuzhou, China.

Ning Wang

Ning Wang is a professor at Department of Neurology and Institute of Neurology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China. He is the head of Fujian Key Laboratory of Molecular Neurology, Fuzhou, China.