Abstract
As a member of spectraplakin family of cytoskeletal crosslinking proteins, microtubule-actin crosslinking factor 1 (MACF1) controls cytoskeleton network dynamics. Knockout of Macf1 in mice resulted in the developmental retardation and embryonic lethality. Spectraplakinopathy type I, a novel neuromuscular condition characterized by periodic hypotonia, lax muscles, joint contracture, and diminished motor skill, was reported to be associated with heterozygous genomic duplication involving the MACF1 loci, with incomplete penetrance and highly variable clinical presentation in a single pedigree. In this study, parental-derived compound heterozygous novel missense mutations of MACF1, c.1517C>T (p.Thr506Ile) and c.11654T>C (p.Ile3885Thr), were found to co-segregate with disease status in two affected brothers presenting with progressive spastic tetraplegia, dystonia, joint contracture, feeding difficulty and developmental delay. We speculated that MACF1 mutations cause spectraplakinopathy inherited in an autosomal recessive manner. Our clinical findings expanded the phenotype of this neuromuscular disorder and provided new insights into the function of MACF1.
Highlights
Spectraplakins act as cytoskeletal crosslinkers by coordinating with three types of cytoskeletal filaments, including microfilaments (F-actin), microtubules, and intermediate filaments, in multicellular organisms [1]
The first report by Jørgensen et al described a proband with periodic hypotonia, lax muscles, joint contractures, and diminished motor skills, which resulted from a heterozygous duplication that covered a large part of the microtubule-actin crosslinking factor 1 (MACF1) gene
The author provided a unique insight and showed that the heterozygous duplication resulted in overall decreased MACF1 gene expression and MACF1 was implicated in the novel myopathy, which they named as spectraplakinopathy type 1
Summary
Spectraplakins act as cytoskeletal crosslinkers by coordinating with three types of cytoskeletal filaments, including microfilaments (F-actin), microtubules, and intermediate filaments, in multicellular organisms [1]. He still could not raise his head, sit up, and stand when he visited our hospital at the age of 8 years He almost manifested a persistent vegetative state because he barely reacted to the outside world. He was born at full term with a birth weight of 3,300 g after an uneventful pregnancy He was referred to the Department of Pediatrics, Peking University First Hospital, at the age of 2 years and 1 month because of psychomotor retardation. High resolution chromosomal karyotyping of the proband showed a normal male karyotype (46, XY)
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