PMID- 10577905
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20220409
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 6
DP  - 1999 Dec
TI  - Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at
      CpG hotspots.
PG  - 1520-9
AB  - Rett syndrome (RTT) is a neurodevelopmental disorder characterized by loss of
      acquired skills after a period of normal development in infant girls. The
      responsible gene, encoding methyl-CpG binding protein 2 (MeCP2), was recently
      discovered. Here we explore the spectrum of phenotypes resulting from MECP2
      mutations. Both nonsense (R168X and R255X) and missense (R106W and R306C)
      mutations have been found, with multiple recurrences. R168X mutations were
      identified in six unrelated sporadic cases, as well as in two affected sisters
      and their normal mother. The missense mutations were de novo and affect conserved
      domains of MeCP2. All of the nucleotide substitutions involve C-->T transitions
      at CpG hotspots. A single nucleotide deletion, at codon 137, that creates a L138X
      stop codon within the methyl-binding domain was found in an individual with
      features of RTT and incontinentia pigmenti. An 806delG deletion causing a V288X
      stop in the transcription-repression domain was identified in a woman with
      motor-coordination problems, mild learning disability, and skewed X inactivation;
      in her sister and daughter, who were affected with classic RTT; and in her
      hemizygous son, who died from congenital encephalopathy. Thus, some males with
      RTT-causing MECP2 mutations may survive to birth, and female heterozygotes with
      favorably skewed X-inactivation patterns may have little or no involvement.
      Therefore, MECP2 mutations are not limited to RTT and may be implicated in a much
      broader phenotypic spectrum.
FAU - Wan, M
AU  - Wan M
AD  - Department of Genetics, Stanford University Medical Center, Stanford, CA
      94305-5323, USA.
FAU - Lee, S S
AU  - Lee SS
FAU - Zhang, X
AU  - Zhang X
FAU - Houwink-Manville, I
AU  - Houwink-Manville I
FAU - Song, H R
AU  - Song HR
FAU - Amir, R E
AU  - Amir RE
FAU - Budden, S
AU  - Budden S
FAU - Naidu, S
AU  - Naidu S
FAU - Pereira, J L
AU  - Pereira JL
FAU - Lo, I F
AU  - Lo IF
FAU - Zoghbi, H Y
AU  - Zoghbi HY
FAU - Schanen, N C
AU  - Schanen NC
FAU - Francke, U
AU  - Francke U
LA  - eng
GR  - HD24448/HD/NICHD NIH HHS/United States
GR  - P01 HD024448/HD/NICHD NIH HHS/United States
GR  - M01 RR000052/RR/NCRR NIH HHS/United States
GR  - RR00052/RR/NCRR NIH HHS/United States
GR  - K12 HD034610/HD/NICHD NIH HHS/United States
GR  - HD24234/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (Codon, Terminator)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MECP2 protein, human)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Alleles
MH  - Amino Acid Substitution/genetics
MH  - *Chromosomal Proteins, Non-Histone
MH  - Codon, Terminator/genetics
MH  - Conserved Sequence
MH  - CpG Islands/*genetics
MH  - DNA Methylation
MH  - DNA-Binding Proteins/chemistry/*genetics
MH  - Dosage Compensation, Genetic
MH  - Female
MH  - Genetic Variation/genetics
MH  - Germ-Line Mutation/genetics
MH  - Humans
MH  - Incontinentia Pigmenti/genetics
MH  - Male
MH  - Methyl-CpG-Binding Protein 2
MH  - Mosaicism/genetics
MH  - Mutation/*genetics
MH  - Nuclear Family
MH  - Pedigree
MH  - Phenotype
MH  - *Repressor Proteins
MH  - Rett Syndrome/diagnosis/*genetics
PMC - PMC1288362
EDAT- 1999/12/01 09:00
MHDA- 2000/03/21 09:00
CRDT- 1999/12/01 09:00
PHST- 1999/12/01 09:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/12/01 09:00 [entrez]
AID - S0002-9297(07)63571-X [pii]
AID - 10.1086/302690 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Dec;65(6):1520-9. doi: 10.1086/302690.