@article {648, title = {Clinical, genetic, and pathologic characterization of Mexican founder mutation c.1387A>G.}, journal = {Neurol Genet}, volume = {5}, year = {2019}, month = {2019 Apr}, pages = {e315}, abstract = {

Objective: To characterize the clinical phenotype, genetic origin, and muscle pathology of patients with the c.1387A>G mutation.

Methods: Standardized clinical data were collected for all patients known to the authors with c.1387A>G mutations in . Muscle biopsies were reviewed and used for histopathology, immunostaining, Western blotting, and DNA extraction. Genetic analysis was performed on extracted DNA.

Results: We report the clinical phenotypes of 6 patients homozygous for the c.1387A>G mutation in . Onset of symptoms was <2 years, and 5 of the 6 patients never learned to walk. Brain MRIs were normal. Cognition was normal to mildly impaired. Microarray analysis of 5 homozygous c.1387A>G patients revealed a 500-kb region of shared homozygosity at 19q13.32, including . All 4 muscle biopsies available for review showed end-stage dystrophic pathology, near absence of glycosylated α-dystroglycan (α-DG) by immunofluorescence, and reduced molecular weight of α-DG compared with controls and patients with homozygous c.826C>A limb-girdle muscular dystrophy.

Conclusions: The clinical features and muscle pathology in these newly reported patients homozygous for c.1387A>G confirm that this mutation causes congenital muscular dystrophy. The clinical severity might be explained by the greater reduction in α-DG glycosylation compared with that seen with the c.826C>A mutation. The shared region of homozygosity at 19q13.32 indicates that c.1387A>G is a founder mutation with an estimated age of 60 generations (\~{}1,200-1,500 years).

}, issn = {2376-7839}, doi = {10.1212/NXG.0000000000000315}, author = {Lee, Angela J and Jones, Karra A and Butterfield, Russell J and Cox, Mary O and Konersman, Chamindra G and Grosmann, Carla and Abdenur, Jose E and Boyer, Monica and Beson, Brent and Wang, Ching and Dowling, James J and Gibbons, Melissa A and Ballard, Alison and Janas, Joanne S and Leshner, Robert T and Donkervoort, Sandra and B{\"o}nnemann, Carsten G and Malicki, Denise M and Weiss, Robert B and Moore, Steven A and Mathews, Katherine D} }