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ARTICLES: J. R. Gorospe, B. S. Singhal, T. Kainu, F. Wu, D. Stephan, J. Trent, E. P. Hoffman, and S. Naidu Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation Neurology 2004; 62: 878-882 [Abstract] [Full text] [PDF]

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Reply to Valk

J. Rafael Gorospe, Bhim S. Singhal, Eric P. Hoffman, and Sakkubai Naidu   (22 June 2004)

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

Jakob Valk   (22 June 2004)

Reply to Valk 22 June 2004
J. Rafael Gorospe, Children's National Medical Center 111 Michigan Ave NW, Washington DC 20010, Bhim S. Singhal, Eric P. Hoffman, and Sakkubai Naidu Send Correspondence to journal: Re: Reply to Valk rgorospe{at}cnmcresearch.org J. Rafael Gorospe, et al.	We thank Dr. Valk for pointing out some historical facts regarding the clinical and molecular characterization of the disease entity called “Megalencephalic leukoencephalopathy with subcortical cysts (MLC).” As he correctly points out, a description of the disease that excluded other disorders associated with megalencephaly and white matter abnormalities was documented in eight patients by van der Knaap et al in the Annals of Neurology in 1995. [1] This was not included in our reference list and was an inadvertent omission on our part. In 1996, Singhal et al reported 35 cases from one ethnic group in India [2], which was a follow-up of their presentation on the Indian Agarwal patients at an international neurology conference in 1991. [3] In addition, the C-insertion mutation in the MLC1 gene was reported in 2002 by Leegwater et al in three Asian Indian MLC patients and was speculated as the founder mutation in the Agarwal community. [4] Our study in 33 Indian MLC patients confirmas that. We agree with Dr. Valk that the credit for advancing our understanding of MLC, as with countless other diseases, rightfully belongs to no single group. References 1) van der Knaap MS, Barth PG, Stroink H et al. Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children. Ann Neurol 1995; 37: 324-334. 2) Singhal BS, Gursahani RD, Udani VP, Biniwale AA. Megalencephalic leukodystrophy in an Asian Indian ethnic group. Pediatr Neurol 1996; 14: 291–296. 3) Singhal BS, Gursahani RD, Biniwale AA, and Udani VP. Megalencephalic leukodystrophy in India (abstract). 8th Asian and Oceanian Congress of Neurology, Tokyo JAPAN, 1991. 4) Leegwater PAJ, Boor PKI, Yuan BQ et al. Identification of novel mutations in MLC1 responsible for megalencephalic leukoencephalopathy with subcortical cysts. Hum Genet 2002; 110: 279–283.
Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation 22 June 2004
Jakob Valk, Radiology VU Medical Center , De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands Send Correspondence to journal: Re: Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation j.valk{at}vumc.nl Jakob Valk	In a recent article, Gorospe et al [1] describe the occurrence of a leukoencephalopathy, commonly called megalencephalic leukoencephalopathy with subcortical cysts (MLC), in an Asian-Indian group, the Agarwals. They describe the clinical and MRI findings in the patients and report on the founder mutation in the gene MLC1, responsible for the disease in this community whcih is an insertion of a C-residue in a stretch of six C-residues in exon 2. The authors refer to the paper on MLC in the Indian community [2] and report that after that the existence of the disease was confirmed in multiple papers on patients of different ethnic backgrounds. I would like to add that the disease was also described in 1953. MLC was detected independently by two groups. [2,3] Although both groups reported their findings at multiple meetings, they did not know about each other’s work. Both should be credited for their original observations. In 2002, Leegwater et al [4] reported the C-insertion in multiple Asian Indian MLC patients and suggested that it was the founder mutation in the Agarwal community. Although Gorospe et al. refer to this paper for the description of mutations, they do not mention that it also reported the Asian-Indian founder mutation. References 1. Gorospe JR, Singhal BS, Kainu T et al. Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation. Neurology 2004; 62: 878-882 2. Singhal BS, Gursahani RD, Udani VP, Biniwale AA. Megalencephalic leukodystrophy in an Asian Indian ethnic group. Pediatr Neurol 1996; 14: 291–296 3. van der Knaap MS, Barth PG, Stroink H, van Nieuwenhuizen O, Arts WF, Hoogenraad F, Valk J. Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children. Ann Neurol 1995; 37: 324-334 4. Leegwater PAJ, Boor PKI, Yuan BQ, et al. Identification of novel mutations in MLC1 responsible for megalencephalic leukoencephalopathy with subcortical cysts. Hum Genet 2002; 110: 279–283