Deleterious mutations in exon 1 of MECP2 in Rett syndrome.
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.
Quenard
Aline
A
Laboratoire de Génétique, EA 3441, CHU Brabois, avenue du Morvan, 54511 Vandoeuvre-les-Nancy cedex, France.
Yilmaz
Saliha
S
Fontaine
Hervé
H
Bienvenu
Thierry
T
Moncla
Anne
A
des Portes
Vincent
V
Rivier
François
F
Mathieu
Michèle
M
Raux
Grégory
G
Jonveaux
Philippe
P
Philippe
Christophe
C
D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D015518:Rett Syndrome / Q000235:genetics*
C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2