Yonsei Med J.  2018 Mar;59(2):337-340. 10.3349/ymj.2018.59.2.337.

FAT1 Gene Alteration in Facioscapulohumeral Muscular Dystrophy Type 1

• Park HJ
• Lee W
• Kim SH
• Lee JH
• Shin HY
• Kim SM
• Park KD
• Lee JH
• Choi YC

• KMID: 2418800
• DOI: http://doi.org/10.3349/ymj.2018.59.2.337

Abstract

Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array. Recent studies revealed that the FAT1 expression is associated with disease activity of FSHD, and the FAT1 alterations result in myopathy with a FSHD-like phenotype. We describe a 59-year-old woman with both contracted D4Z4 repeat units and a FAT1 mutation. Shoulder girdle muscle weakness developed at the age of 56 years, and was followed by proximal leg weakness. When we examined her at 59 years of age, she displayed asymmetric and predominant weakness of facial and proximal muscles. Muscle biopsy showed increased variation in fiber size and multifocal degenerating fibers with lymphocytic infiltration. Southern blot analysis revealed 8 D4Z4 repeat units, and targeted sequencing of modifier genes demonstrated the c.10331 A>G variant in the FAT1 gene. This FAT1 variant has previously been reported as pathogenic variant in a patient with FSHD-like phenotype. Our study is the first report of a FAT1 mutation in a FSHD1 patient, and suggests that FAT1 alterations might work as a genetic modifier.

Keyword

Facioscapulohumeral muscular dystrophies; muscular dystrophy; FAT1

MeSH Terms

Cadherins/*genetics
Female
Humans
Magnetic Resonance Imaging
Middle Aged
Muscles/pathology
Muscular Dystrophy, Facioscapulohumeral/diagnostic imaging/*genetics/pathology
Mutation/*genetics
Phenotype
Cadherins

Figure

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  Fig. 1 Histopathological results and T1-weighted MR images of whole body. (A) Hematoxylin and eosin (H-E) staining revealed increased variation in fiber size and multifocal degenerating fibers with lymphocytic infiltration. (B) Modified Gomori-trichrome (GT) staining did not reveal any intracytoplasmic inclusions and subsarcolemmal depositions. (C) Staining with reduced nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-tr) showed mild disorganization of intermyofibrillar network. (A, H-E stain, ×200; B, modified GT stain, ×100; and C, NADH-tr stain, ×100). (D-G) T1-weighted MR images of whole body. (D) At the upper arm level, biceps brachii muscles were shown to be predominantly affected on the right side (white arrows). (E) At the abdominal level, both abdominal (black arrow heads) and paraspinal (black arrows) muscles were found to be totally replaced by fat tissues. (F) At the thigh levels, semitendinosus, semimembranosus, biceps femoris, vastus medialis, and vastus intermedius muscles were totally replaced by the fat tissue. Rectus femoris muscles were shown to be severely affected on the right side (white arrow heads). (G) At the calf level, bilateral soleus muscles were shown to be predominantly affected.

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