We identified three non-related patients manifesting a childhood-onset progressive neuromyopathy with congenital cataracts, delayed walking, distal weakness and wasting, glaucoma and swallowing difficulties. Electrophysiology and nerve biopsies showed a mixed axonal and demyelinating neuropathy, while muscle biopsy disclosed both neurogenic and myopathic changes with ragged red fibers, and muscle MRI showed consistent features across patients, with a peculiar concentric disto-proximal gradient of fatty replacement. We used targeted next generation sequencing and candidate gene approach to study these families. Compound biallelic heterozygous variants, p.[(Pro648Arg)]; [(His932Tyr)] and p.[(Thr251Ile),(Pro587Leu)]; [(Arg943Cys)], were found in the three patients causing this homogeneous phenotype. Our report on a subset of unrelated patients, that showed a distinct autosomal recessive childhood-onset neuromyopathy with congenital cataracts and glaucoma, expands the clinical spectrum of POLG-related disorders. It also confirms the association between cataracts and neuropathy with variants in POLG. Early onset cataract is otherwise rare in POLG-related disorders and so far reported only in a few patients with the clinical pattern of distal myopathy or neuromyopathy.
|Titolo:||Neuromyopathy with congenital cataracts and glaucoma: A distinct syndrome caused by POLG variants|
|Citazione:||Castiglioni, C., Fattori, F., Udd, B., De Los Angeles Avaria, M., Suarez, B., D'Amico, A., et al. (2018). Neuromyopathy with congenital cataracts and glaucoma: A distinct syndrome caused by POLG variants. EUROPEAN JOURNAL OF HUMAN GENETICS, 26(3), 367-373.|
|Appare nelle tipologie:||1.1 Articolo in rivista|