A novel MYH7 mutation occurring independently in French and Norwegian Laing distal myopathy families and de novo in one Finnish patient

Abstract

Laing early-onset distal myopathy is a rare autosomal dominant myopathy and caused by mutations in the MYH7 gene, encoding the slow beta myosin heavy chain. We report the first molecularly verified Laing distal myopathy in a French family caused by a novel p.Glu1508del mutation in the MYH7 gene. Interestingly, we identified the identical mutation in an unrelated Norwegian family and, as a de novo mutation, in one sporadic Finnish patient. Described in detail are the clinical and electrophysiological characteristics of 5 patients from the French family. The phenotype in the Finnish patient and the Norwegian patients is largely similar. This mutation causes a benign myopathy within the range of previously reported Laing myopathy phenotype variations. Onset of weakness in the tibialis anterior (TA) muscles occurred in early childhood in all patients. Finger extensor and neck flexor weakness together with Achilles tendon retractions were other frequent findings. The independent recurrence of the identical mutation without any founder background may reflect a mutational susceptibility of this residue, in accordance with some other MYH7 mutations previously reported. De novo mutations seem to be frequent in Laing distal myopathy. This is of clinical importance since a dominant family history is missing, which may confuse differential diagnostic efforts.

A rare mutation in MYH7 gene occurs with overlapping phenotype

“…We identified an Italian family with a mutation of the MYH7 gene sited in the distal rod of the protein, which presents with a very complex overlapping syndrome characterized by non compaction cardiomyopathy, LDM like phenotype with early and markedly proximal involvement and FTD picture at muscle biopsy. The mutation c.5401G > A (p.Glu1801Lys) has never been described in an Italian family whereas has been reported by Dubourg O et al in two families, one from France and another from Norway, and in a Finnish sporadic case [12]. All the affected patients have similar clinical pictures, compatible with LDM phenotype.…”

Laing distal myopathy with a novel mutation in exon 34 of the MYH7 gene

“…Such a pattern has also been described previously (4,12,17). However, isolated fatty degeneration of the tibialis anterior muscle is not specific for Laing myopathy.…”

“…There have been only a few families encountered worldwide with genetically proven Laing myopathy (1, 2,3,4,6,7,9,10,11,12,13,14,16). Here, we describe a four-generation family with four affected members in 2 generations with Laing myopathy and additional features with a mutation in exon 34 of the MYH7 gene that has not as been reported so far.…”

“…All of these mutations are localized in the rod domain of the protein . Cases have been described from Australia, Central Europe, and USA(2,3,4, 6,7,10,11,12,13,14,15). Only while the present paper was under consideration already, a larger cohort of 21 families with 12 novel mutations originating from several countries and three continents has been published(9).…”

A novel MYH7 Leu1453pro mutation resulting in Laing distal myopathy in an Irish family

“…Three phenotypes are associated with involvement of different regions of the MYH7 gene, namely Laing distal myopathy (exons 32-36), myosin storage myopathy (exons 37-40) and familial hypertrophic/dilated cardiomyopathy (exons 3-28 but can be spread along the gene). Recent publications have expanded the clinical spectrum of LDM ranging from asymptomatic hyperCKemia, proximal (limb-girdle), axial and respiratory involvement to the classical distal and scapuloperoneal phenotype [2][3][4][5][6][7]. Here we describe clinical, pathological, imaging and genetic findings of a large Irish family with a novel heterozygous mutation L1453P in the MYH7 gene.…”