Patterns of Pregnancy Loss, Perinatal Mortality, and Postneonatal Childhood Deaths in Families of Girls With Rett Syndrome

Fyfe, Sue; Leonard, Helen; Dye, Danielle E.; Leonard, Seonaid

doi:10.1177/088307389901400706

Cited by 14 publications

(5 citation statements)

References 15 publications

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“…Moreover, several studies have shown no increase in parental age, 18,19 or in spontaneous abortions rate among sibs. 20,21 It is not surprising, because such skewed sex ratio might be expected only when the mother is a healthy carrier of the MECP2 mutation (perhaps spared by a skewed, favourable pattern of X inactivation) or bears the mutation in a mosaic state. Moreover, the sex limited expression of Rett syndrome is not complete.…”

Section: Discussionmentioning

confidence: 99%

Parental origin of de novo MECP2 mutations in Rett syndrome

Girard¹,

Couvert²,

Carrié³

et al. 2001

Eur J Hum Genet

109

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Rett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively in females as sporadic cases. Recently, DNA mutations in the MECP2 gene have been detected in approximately 70% of patients with RTT. To explain the sex-limited expression of RTT, it has been suggested that de novo X-linked mutations occur exclusively in male germ cells resulting therefore only in affected daughters. To test this hypothesis, we have analysed 19 families with RTT syndrome due to MECP2 molecular defects. In seven informative families we have found by DHPLC a nucleotide variant which could be used to differentiate between the maternal and the paternal allele. In each subject investigated from these families, we have amplified specifically each allele and sequenced allele-specific PCR products to identify the allele bearing the mutation as well as the parental origin of each X chromosome. This approach allowed us to determine the parental origin of de novo mutations in all informative families. In five cases, the de novo MECP2 mutations have a paternal origin and in the two other cases a maternal origin. In all transitions at CpG, the de novo mutation observed was of paternal origin. The high frequency of male germ-line transmission of the mutation (71% of RTT informative cases) is consistent with a predominant occurrence of the disease in females. European Journal of Human Genetics (2001) 9, 231 ± 236.

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Section: Discussionmentioning

confidence: 99%

Parental origin of de novo MECP2 mutations in Rett syndrome

Girard¹,

Couvert²,

Carrié³

et al. 2001

Eur J Hum Genet

109

View full text Add to dashboard Cite

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“…Generalised estimating equations that take into account the correlation between family members can then be used for this purpose. 29 Our study, using the methods described, has been a first attempt to identify patterns of perinatal death 47 and familial aggregation 48 in families of girls with Rett syndrome. It systematically collected data from a whole juvenile population and compared results with a control group.…”

Section: Discussionmentioning

confidence: 99%

Study methodology. Using genetic epidemiology to study Rett syndrome: the design of a case–control study

Leonard

Fyfe

Dye

et al. 2000

Paediatric Perinatal Epid

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Rett syndrome is a neurological disorder that is seen almost exclusively in females. Although generally considered to have a genetic basis, the underlying mechanism remains obscure. One favoured hypothesis is that the syndrome is an X-linked dominant disorder, lethal or non-expressed in males. Genealogical research has also suggested that the mode of transmission in Rett syndrome may involve a premutation which over several generations is converted to a full mutation. Geographical clustering has been reported, and it has also been proposed that Rett syndrome is a clinically variable condition and that other neurological disorders may be occurring more commonly in families with Rett syndrome. Other studies have found an apparent increase in intellectual disability and seizures in the extended families of girls with Rett syndrome. The science of genetic epidemiology can be used to identify familial aggregation, which is the clustering of a disorder within a family. We have used a case-control study design to investigate both fetal wastage and familial aggregation of other disorders in families of girls with Rett syndrome. The Australian Rett Syndrome Database provided the source of cases, and control probands were girls of a similar age with normal development. This paper describes the methodology for a case-control study of this rare condition using pedigree data and discusses issues in the collection and evaluation of such data. The use of a control population is an important feature. Both the strengths and the shortcomings of our design are identified, and recommendations are made for future research.

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“… 3 Three families were described in which sudden infant death syndrome deaths had occurred in other siblings. 12 In a North American survey of Rett syndrome, 13 43% of extended families had a child with an intellectual disability and Down syndrome was stated as one of the most frequent presentations. As the most common known cause of intellectual disability 14 this might be expected.…”

Section: Discussionmentioning

confidence: 99%

Family data in Rett syndrome: Association with other genetic disorders

Leonard

Fyfe

Dye

et al. 2000

J Paediatrics Child Health

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Mutations in the MECP2 gene have now been reported in a proportion of sporadic cases. Thus, it will be important to examine this phenotype-genotype correlation in the Australian cohort. Where a mutation is found, prenatal diagnosis in a subsequent pregnancy will be a possibility. Using the Australian population database and in conjunction with the clinical genetic services in each state it is planned to contact families with an affected girl to offer testing and counselling.

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Patterns of Pregnancy Loss, Perinatal Mortality, and Postneonatal Childhood Deaths in Families of Girls With Rett Syndrome

Cited by 14 publications

References 15 publications

Parental origin of de novo MECP2 mutations in Rett syndrome

Parental origin of de novo MECP2 mutations in Rett syndrome

Study methodology. Using genetic epidemiology to study Rett syndrome: the design of a case–control study

Family data in Rett syndrome: Association with other genetic disorders

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