Exome sequencing of two patients in a family with atypical X-linked leukodystrophy
Article first published online: 21 JUN 2011
© 2011 John Wiley & Sons A/S
Special Issue: Exome Sequencing
Volume 80, Issue 2, pages 161–166, August 2011
How to Cite
Tsurusaki, Y., Okamoto, N., Suzuki, Y., Doi, H., Saitsu, H., Miyake, N. and Matsumoto, N. (2011), Exome sequencing of two patients in a family with atypical X-linked leukodystrophy. Clinical Genetics, 80: 161–166. doi: 10.1111/j.1399-0004.2011.01721.x
- Issue published online: 12 JUL 2011
- Article first published online: 21 JUN 2011
- Accepted manuscript online: 3 JUN 2011 12:06PM EST
- Received 4 May 2011, revised and accepted for publication 31 May 2011
- atypical phenotype;
- exome sequencing;
- X-linked leukodystrophy
Tsurusaki Y, Okamoto N, Suzuki Y, Doi H, Saitsu H, Miyake N, Matsumoto N. Exome sequencing of two patients in a family with atypical X-linked leukodystrophy.
We encountered a family with two boys similarly showing brain atrophy with reduced white matter, hypoplasia of the brain stem and corpus callosum, spastic paralysis, and severe growth and mental retardation without speaking a word. The phenotype of these patients was not compatible with any known type of syndromic leukodystrophy. Presuming an X-linked disorder, we performed next-generation sequencing (NGS) of the transcripts of the entire X chromosome. A single lane of exome NGS in each patient was sufficient. Six potential mutations were found in both affected boys. Two missense mutations, including c.92T>C (p.V31A) in L1CAM, were potentially pathogenic, but this remained inconclusive. The other four could be excluded. Because the patients did not show adducted thumbs or hydrocephalus, the L1CAM change in this family can be interpreted as different scenarios. Personal genome analysis using NGS is certainly powerful, but interpretation of the data can be a substantial challenge requiring a lot of tasks.