Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation

J. R. Gorospe, B. S. Singhal, T. Kainu, F. Wu, D. Stephan, J. Trent, E. P. Hoffman, S. Naidu

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)878-882
Number of pages5
JournalNeurology
Volume62
Issue number6
StatePublished - Mar 23 2004

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Cysts
Mutation
Megalencephaly
Ethnic Groups
India
Exons
Genes
Founder Effect
Cytosine
Ataxia
Introns
Seizures
DNA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Gorospe, J. R., Singhal, B. S., Kainu, T., Wu, F., Stephan, D., Trent, J., ... Naidu, S. (2004). Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation. Neurology, 62(6), 878-882.

Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation. / Gorospe, J. R.; Singhal, B. S.; Kainu, T.; Wu, F.; Stephan, D.; Trent, J.; Hoffman, E. P.; Naidu, S.

In: Neurology, Vol. 62, No. 6, 23.03.2004, p. 878-882.

Research output: Contribution to journalArticle

Gorospe, JR, Singhal, BS, Kainu, T, Wu, F, Stephan, D, Trent, J, Hoffman, EP & Naidu, S 2004, 'Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation', Neurology, vol. 62, no. 6, pp. 878-882.
Gorospe JR, Singhal BS, Kainu T, Wu F, Stephan D, Trent J et al. Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation. Neurology. 2004 Mar 23;62(6):878-882.
Gorospe, J. R. ; Singhal, B. S. ; Kainu, T. ; Wu, F. ; Stephan, D. ; Trent, J. ; Hoffman, E. P. ; Naidu, S. / Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation. In: Neurology. 2004 ; Vol. 62, No. 6. pp. 878-882.
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AU - Singhal, B. S.

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AU - Wu, F.

AU - Stephan, D.

AU - Trent, J.

AU - Hoffman, E. P.

AU - Naidu, S.

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N2 - 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.

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