Abstract
FSHD2 is a rare form of facioscapulohumeral muscular dystrophy (FSHD) characterized
by the absence of a contraction in the D4Z4 macrosatellite repeat region on chromosome
4q35 that is the hallmark of FSHD1. However, hypomethylation of this region is common
to both subtypes. Recently, mutations in SMCHD1 combined with a permissive 4q35 allele were reported to cause FSHD2. We identified
a novel p.Lys275del SMCHD1 mutation in a family affected with FSHD2 using whole-exome sequencing and linkage
analysis. This mutation alters a highly conserved amino acid in the ATPase domain
of SMCHD1. Subject III-11 is a male who developed asymmetrical muscle weakness characteristic
of FSHD at 13 years. Physical examination revealed marked bilateral atrophy at biceps brachii, bilateral
scapular winging, some asymmetrical weakness at tibialis anterior and peroneal muscles,
and mild lower facial weakness. Biopsy of biceps brachii in subject II-5, the father
of III-11, demonstrated lobulated fibers and dystrophic changes. Endomysial and perivascular
inflammation was found, which has been reported in FSHD1 but not FSHD2. Given the
previous report of SMCHD1 mutations in FSHD2 and the clinical presentations consistent with the FSHD phenotype,
we conclude that the SMCHD1 mutation is the likely cause of the disease in this family.
Keywords
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Article info
Publication history
Published online: October 14, 2013
Accepted:
August 19,
2013
Received in revised form:
July 24,
2013
Received:
April 29,
2013
Identification
Copyright
© 2013 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
