Prenatal diagnosis in Rett syndrome.
OBJECTIVE
Rett syndrome (RTT) is an X-linked neurodevelopmental dominant disorder that affects almost exclusively girls. The disease is mainly sporadic, caused by de novo mutations at MECP2 gene (Xq28), but a low percentage of familial cases have been reported. We present the results of RTT prenatal diagnosis in three families and discuss the usefulness of such analyses in diseases caused mainly by de novo mutations.


METHODS
For adult individuals, DNA was extracted from peripheral lymphocytes; for fetus analysis it was obtained from cultured amniotic fluid or from chorionic biopsy specimens. Mutation detection at MECP2 gene was first carried out in the patients by SSCP/HD analysis and subsequent sequencing. Family studies and prenatal diagnoses were done by direct analysis of previously characterized patients' mutations using SSCP/HD or restriction analysis.


RESULTS
Heterozygous mutations identified in the 3 patients were: 1061del96bp, 473C-->T, and 763C-->T, respectively. Mutations were not present in the mothers' DNAs obtained from peripheral lymphocytes. None of the 3 fetuses analyzed carried the mutation of the affected sister.


CONCLUSIONS
Recurrence within RTT families can be due to asymptomatic nonpenetrant carrier mothers or to parental germinal mosaicism for the MECP2 mutation. Since germline mosaicism can neither be predicted nor detected, families with 1 affected patient whose RTT-causing mutation has been previously identified can benefit from prenatal diagnosis which contributes to a decrease in the recurrence risk in a new pregnancy comparable to that of the normal population.
Armstrong
J
J
Genetics Section, University Hospital Sant Joan de Déu, Av. Sant Joan de Déu 2, E-89050 Esplugues, Barcelona, Spain.
Aibar
E
E
Pineda
M
M
Pérez
M M
MM
Geán
E
E
Carrera
M
M
Casas
C
C
Martínez
F
F
Monrós
E
E
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005817:Genetic Counseling; D018095:Germ-Line Mutation; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2; D009030:Mosaicism; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012097:Repressor Proteins; D015518:Rett Syndrome / Q000175:diagnosis* / Q000235:genetics*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins