Limb-Girdle Muscular Dystrophy R9 due to a Novel Complex Insertion/Duplication Variant in FKRP Gene

Erin Willis; Steven A Moore; Mary O Cox; Vikki Stefans; Akilandeswari Aravindhan; Murat Gokden; Aravindhan Veerapandiyan

doi:10.1177/2329048X221097518

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Limb-Girdle Muscular Dystrophy R9 due to a Novel Complex Insertion/Duplication Variant in FKRP Gene

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Limb-Girdle Muscular Dystrophy R9 due to a Novel Complex Insertion/Duplication Variant in FKRP Gene

Erin Willis, Steven A Moore, Mary O Cox, Vikki Stefans, Akilandeswari Aravindhan, Murat Gokden and Aravindhan Veerapandiyan

Child neurology open, Vol.9, p.2329048X221097518

04/2022

DOI: 10.1177/2329048X221097518

PMCID: PMC9087226

PMID: 35557983

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Abstract

Limb-girdle muscular dystrophy R9 (LGMD2I, LGMDR9) is an autosomal recessive disorder caused by pathogenic variants in the fukutin-related protein ( ) gene. We describe a 17 year old boy with LGMDR9 whose symptoms began at age 5 years. Muscle histopathology, immunostaining, and western blotting were consistent with a dystroglycanopathy. Genetic testing identified maternal inheritance of the most common pathogenic variant c.826C>A (p.L276I). Also detected was a novel insertion and duplication on the paternally inherited allele: a single nucleotide insertion (c.948_949insC) and an eighteen nucleotide duplication (c.999_1017dup18) predicted to result in premature translation termination (p.E389*). Based on the clinical features and course of the patient, heterozygosity for the common pathogenic variant, and abnormal glycosylation of alpha-dystroglycan, we suggest that the novel insertion and duplication are pathogenic. This case expands the genetic heterogeneity of LGMDR9 and emphasize the importance of muscle biopsy for precise diagnosis.

LGMD

weakness

LGMD 21

FKRP

dystroglycanopathy

Details

Title: Subtitle: Limb-Girdle Muscular Dystrophy R9 due to a Novel Complex Insertion/Duplication Variant in FKRP Gene
Creators: Erin Willis - University of Arkansas for Medical Sciences
Steven A Moore - University of Iowa
Mary O Cox - University of Iowa
Vikki Stefans - University of Arkansas for Medical Sciences
Akilandeswari Aravindhan - University of Arkansas for Medical Sciences
Murat Gokden - University of Arkansas for Medical Sciences
Aravindhan Veerapandiyan - University of Arkansas for Medical Sciences
Resource Type: Journal article
Publication Details: Child neurology open, Vol.9, p.2329048X221097518
DOI: 10.1177/2329048X221097518
PMID: 35557983
PMCID: PMC9087226
NLM abbreviation: Child Neurol Open
ISSN: 2329-048X
Language: English
Date published: 04/2022
Academic Unit: Pathology
Record Identifier: 9984267241802771

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