Eur J Med Genet. 2006 Jul-Aug;49(4):313-22. Epub 2005 Dec 20.
Deleterious mutations in exon 1 of MECP2 in Rett syndrome
Quenard A, Yilmaz S, Fontaine H, Bienvenu T, Moncla A, des Portes V, Rivier F, Mathieu M, Raux G, Jonveaux P, Philippe C.
Laboratoire de genetique, EA 3441, CHU Brabois, avenue du Morvan, 54511 Vandoeuvre-les-Nancy cedex, France.Abstract
The MECP2 gene is responsible for 80-85% of typical cases of Rett syndrome with deleterious mutations affecting exons 3 and 4. Recently, an alternate transcript including exon 1 was discovered with a new protein isoform (MeCP2_e1) much more abundant in brain. We screened exon 1 of MECP2 for mutations and for large rearrangements in a panel of 212 typical cases of Rett syndrome and one family case with atypical Rett syndrome. We identified two deleterious mutations (c.48_55dup and c.62+2_62+3del) and four large rearrangements encompassing exon 1 of MECP2. We also identified the c.16_21dup alteration formerly reported as c.3_4insGCCGCC and give additional support to classify this sequence variation as polymorphic. In our large panel of typical Rett, mutations affecting exon 1 of MECP2 represent 1% of the deleterious alleles. This study confirms that mutations in exon 1 of MECP2 are a rare cause of Rett syndrome.
Lay Summary
The MECP2 gene can be thought of as a book with four chapters. Mutations may include having a missing page(s), an extra page(s) or pages in the wrong order. In some cases an entire chapter or two chapters may be missing. The correct term for the chapters is exons.
Until March of 2004 it was thought that only mutations in exons 2-3-4 could lead to Rett Syndrome. In March of 2004 the Bird lab and the Minassian lab announced the discovery of a new form of MeCP2. The new protein, which is 3% longer then the original form, is ten times more abundant in the brain. This longer section is called exon 1. This study analyzed blood samples of 212 individuals with Rett symptoms but no identifiable mutations in MECP2. They found mutations in exon 1, although Rett, are a cause of Rett Syndrome.