Neuropediatrics 2006; 37 - MP49
DOI: 10.1055/s-2006-943646

MUTATIONS IN POMT1 AND POMGNT1 IN ITALIAN CHILDREN WITH CMD

E Bertini 1, C Bruno 2, A D'Amico 1, R Biancheri 2, A Tessa 1, A Falace 2, M Pedemonte 2, E Mercuri 3, C Minetti 2, FM Santorelli 1
  • 1Molecular Medicine, IRCCS Bambino Gesù Hospital, Rome, Italy
  • 2Neurogenetics & Neurodegenerative Diseases, IRCCS Gaslini Institute, Genova, Italy
  • 3Neuropediatrics, Catholic University, Rome, Italy

Objectives: To report clinical, morphological, and molecular features in Italian children with CMD and glycosylation defects.

Background: Congenital muscular dystrophies (CMD) due to mutations in genes encoding proven or putative glycosyltransferases are named disorders of O-glycosylation or alpha-dystroglycanopathies. This group includes Walker-Warburg syndrome due to mutations in POMT1 and POMT2; muscle-eye-brain (MEB) disease due to mutations in POMGnT1; Fukuyama CMD caused by mutations in fukutin; CMD type 1C caused by mutations in FKRP, and CMD type 1D secondary to mutations in LARGE.

Methods: Clinical and neurophysiological evaluations, immunohistochemical studies and molecular genetic analyses were performed in 12 children with CMD and glycosylation defects.

Results: We identified new POMT1 mutations in three unrelated Italian patients with severe motor impairment, leg hypertrophy, and mental retardation but without brain and ocular malformations. These patients are similar to those described with limb girdle muscular dystrophy and mental retardation (LGMD2K) but have earlier onset and more severe motor disability. Moreover, we identified three novel variants in POMGnT1: two subjects showed a classic MEB phenotype whereas one patient presents muscle and brain involvement only.

Conclusion: Our findings further expand the spectrum of clinical phenotypes associated with CMD associated with an O-glycosylation defect and enlarge the array of mutations in POMT1 and POMGnT1.