A Rett syndrome MECP2 mutation that causes mental retardation in men.
OBJECTIVE
To characterize the clinical features of a new type of X-linked mental retardation associated with MECP2 mutation in the index family.


BACKGROUND
MECP2 mutations, originally described in a high percentage of patients with classic Rett syndrome, were considered lethal in men. The authors recently described a novel A140V MECP2 missense mutation in an Italian family with X-linked semidominant mental retardation.


METHODS
The neurologic features of six symptomatic relatives (two women and four men) carrying the mutation were compiled. Laboratory investigations included EEG, EMG, conduction velocity (CV) of peripheral nerves, brain MRI, and (1)H-MR spectroscopy.


RESULTS
Mental retardation and signs of neurologic impairment were present in all the affected members, but more pronounced in men. Neurologic features included slowly progressive spastic paraparesis/pyramidal signs (6/6), distal atrophy of the legs (6/6), ataxia (2/6), and postural tremor of the hands (3/6). Speech was preserved (6/6) but was dysarthric in the oldest brothers (2/6). Mild dysmorphic features were present in all cases.


CONCLUSIONS
The neurologic disorder associated with A140V MECP2 mutation is not necessarily lethal in men, but they are more severely affected than women of the same family.
Dotti
M T
MT
Neurometabolic Unit and Center for the Diagnosis Prevention and Therapy of Neuro-handicap, University of Siena, Italy. dotti@unisi.it
Orrico
A
A
De Stefano
N
N
Battisti
C
C
Sicurelli
F
F
Severi
S
S
Lam
C W
CW
Galli
L
L
Sorrentino
V
V
Federico
A
A
D000328:Adult; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012097:Repressor Proteins; D015518:Rett Syndrome / Q000235:genetics* / Q000503:physiopathology
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins