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Large genomic deletions: A novel cause of Ullrich congenital muscular dystrophy
Author(s) -
Foley A. Reghan,
Hu Ying,
Zou Yaqun,
Yang Michele,
Medne Līvija,
Leach Meganne,
Conlin Laura K.,
Spinner Nancy,
Shaikh Tamim H.,
Falk Marni,
Neumeyer Ann M.,
Bliss Laurie,
Tseng Brian S.,
Winder Thomas L.,
Bönnemann Carsten G.
Publication year - 2011
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.22283
Subject(s) - muscular dystrophy , congenital muscular dystrophy , genetics , medicine , biology
Two mutational mechanisms are known to underlie Ullrich congenital muscular dystrophy (UCMD): heterozygous dominant negatively‐acting mutations and recessively‐acting loss‐of‐function mutations. We describe large genomic deletions on chromosome 21q22.3 as a novel type of mutation underlying recessively inherited UCMD in 2 families. Clinically unaffected parents carrying large genomic deletions of COL6A1 and COL6A2 also provide conclusive evidence that haploinsufficiency for COL6A1 and COL6A2 is not a disease mechanism for Bethlem myopathy. Our findings have important implications for the genetic evaluation of patients with collagen VI–related myopathies as well as for potential therapeutic interventions for this patient population. Ann Neurol 2011;69:206–211