| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Research Center for Genetic Medicine (Drs. Gorospe, Wu, Stephan, and Hoffman), Children’s National Medical Center, Washington, DC, and National Human Genome Research Institute (Drs. Kainu and Trent), NIH, Bethesda, and Neurogenetics Unit (Dr. Naidu), Kennedy Krieger Institute, Baltimore, MD; and Department of Neurology (Dr. Singhal), Bombay Hospital Institute of Medical Sciences, India.
Address correspondence and reprint requests to Dr. J.R. Gorospe, Research Center for Genetic Medicine, Children’s National Medical Center, 111 Michigan Ave. NW, Washington, DC 20010; e-mail: rgorospe{at}cnmcresearch.org
Background: A distinct clinical syndrome characterized by megalencephaly, mild to moderate cognitive decline, slowly progressive spasticity, ataxia, occasional seizures, and extensive white matter changes with temporal cysts by imaging studies has been described in a particular ethnic group (Agarwals) in India. This disorder is very similar to megalencephalic leukoencephalopathy with subcortical cysts (MLC), a newly characterized leukodystrophy whose molecular basis was recently shown to be mutations in a gene (KIAA0027) that has been renamed MLC1.
Objective: To determine if this disorder among the Agarwals is due to mutations in MLC1 by a mutation screening study conducted on affected Agarwal patients.
Methods: Genomic DNA from these Indian leukodystrophy patients was screened for mutations in the entire coding region, including the exon–intron boundaries, of the MLC1 gene.
Results: Thirty-three affected individuals whose clinical and imaging presentations were consistent with MLC were screened. All were from northern India and included 31 known Agarwals, 1 non-Agarwal, and 1 adopted patient whose ethnicity is unknown. All 31 Agarwal patients tested positive for a homozygous insertion of a cytosine in exon 2. The adopted patient was homozygous for A157E. No mutation in the coding region was found in the non-Agarwal patient.
Conclusions: Indian patients with megalencephaly and MRI changes that show extensive white matter changes with temporal cysts should raise suspicion for MLC. Members of the Agarwal ethnic group affected with the disorder present with a mildly progressive course and show a common mutation (320insC) in the MLC1 gene, suggesting a founder effect.
Received August 22, 2003. Accepted in final form November 18, 2003.
This article has been cited by other articles:
|
|
 |
|
  M. Henneke, N. Preuss, V. Engelbrecht, F. Aksu, E. Bertini, G. Bibat, K. Brockmann, C. Hubner, M. Mayer, V. Mejaski-Bosnjak, et al. Cystic leukoencephalopathy without megalencephaly: A distinct disease entity in 15 children Neurology, April 26, 2005; 64(8): 1411 - 1416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Valk, J. R. Gorospe, B. S. Singhal, E. P. Hoffman, and S. Naidu Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation Neurology, December 14, 2004; 63(11): 2197 - 2197. [Full Text] [PDF]
|
|
|
|
 |
|
 O. Teijido, A. Martinez, M. Pusch, A. Zorzano, E. Soriano, J. A. del Rio, M. Palacin, and R. Estevez Localization and functional analyses of the MLC1 protein involved in megalencephalic leukoencephalopathy with subcortical cysts Hum. Mol. Genet., November 1, 2004; 13(21): 2581 - 2594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Leukodystrophies Diagnosed by Molecular Genetic Studies Journal Watch Neurology, June 11, 2004; 2004(611): 2 - 2. [Full Text]
|
|
|
|
|
|
M. J. Noetzel Diagnosing "undiagnosed" leukodystrophies: The role of molecular genetics Neurology, March 23, 2004; 62(6): 847 - 848. [Full Text] [PDF]
|
|
Read all Correspondence
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
