Article title
Hardwick SA, Reuter K, Williamson SL, Vasudevan V, Donald J, Slater K, Bennetts B, Bebbington A, Leonard H, Williams SR, Smith RL, Cloosterman D, Christodoulou J. Delineation of large deletions of the MECP2 gene in Rett syndrome patients, including a familial case with a male proband. European Journal of Human Genetics. 2007 Dec;15(12):1218-29. Download snapshot see article abstract.
Background
Recently, a new genetic testing technique has allowed the detection of a mutation called a large deletion which is where a part of the MECP2 gene is deleted. A large deletion can be associated with clinical signs of Rett syndrome.
What did we do
We used multiplex ligation-dependent probe amplification to examine the MECP2 gene sequences in 149 girls and 1 boy who had clinical Rett syndrome but previous genetic testing for a MECP2 had been negative. We also described the genetic structure in detail including the level of X-chromosome inactivation.
What we found
Eleven girls and one boy were found to have a large deletion. Four of the 11 girls in this group had a high degree of X-inactivation. Included in this group were a brother and a sister pair, both of whom showed signs of Rett syndrome. The size of the deletion was not significantly associated with severity of symptoms and girls with either typical or atypical presentations of Rett syndrome had deletions of similar sizes. When compared to girls with other common mutations (but not a large deletion), those with a large deletion appeared to have more severe clinical symptoms.
What does it mean
Testing for this mutation can allow for genetic confirmation of Rett syndrome in some cases who tested negatively to usual testing techniques. Examination of a larger number of cases will help to define the clinical presentation associated with this mutation.