Article Text

Prevalence of Prader-Willi and Angelman syndromes among mentally retarded boys in Brazil
  1. ANDRÉIA M L VERCESI
  1. Department of Biochemistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
  2. Department of General Biology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
  3. Department of Paediatrics, Universidade Federal de Minas Gerais, and GENE - Núcleo de Genética Médica, Belo Horizonte, MG, Brazil
  4. Departmento de Bioquímica e Imunologia, Instituto de Ciências Biológicas-UFMG, Av Antônio Carlos 6627, 31.270-901 Belo Horizonte, MG, Brazil, and GENE - Núcleo de Genética Médica, Belo Horizonte, MG, Brazil
    1. MARIA RAQUEL S CARVALHO
    1. Department of Biochemistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
    2. Department of General Biology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
    3. Department of Paediatrics, Universidade Federal de Minas Gerais, and GENE - Núcleo de Genética Médica, Belo Horizonte, MG, Brazil
    4. Departmento de Bioquímica e Imunologia, Instituto de Ciências Biológicas-UFMG, Av Antônio Carlos 6627, 31.270-901 Belo Horizonte, MG, Brazil, and GENE - Núcleo de Genética Médica, Belo Horizonte, MG, Brazil
      1. MARCOS J B AGUIAR
      1. Department of Biochemistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
      2. Department of General Biology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
      3. Department of Paediatrics, Universidade Federal de Minas Gerais, and GENE - Núcleo de Genética Médica, Belo Horizonte, MG, Brazil
      4. Departmento de Bioquímica e Imunologia, Instituto de Ciências Biológicas-UFMG, Av Antônio Carlos 6627, 31.270-901 Belo Horizonte, MG, Brazil, and GENE - Núcleo de Genética Médica, Belo Horizonte, MG, Brazil
        1. SÉRGIO D J PENA
        1. Department of Biochemistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
        2. Department of General Biology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
        3. Department of Paediatrics, Universidade Federal de Minas Gerais, and GENE - Núcleo de Genética Médica, Belo Horizonte, MG, Brazil
        4. Departmento de Bioquímica e Imunologia, Instituto de Ciências Biológicas-UFMG, Av Antônio Carlos 6627, 31.270-901 Belo Horizonte, MG, Brazil, and GENE - Núcleo de Genética Médica, Belo Horizonte, MG, Brazil

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          Editor—Prader-Willi (PWS) and Angelman syndromes (AS) are caused by paternal or maternal deletions in 15q11-q13 respectively. Although diagnosis of these diseases may occasionally be made by high resolution chromosomal studies, it is best achieved using FISH or parent of origin analysis on Southern blots. To establish the prevalence of PWS and AS in the general population or among mentally retarded subjects, we need easy, rapid, and low cost screening procedures. In the July 1998 issue of the Journal of Medical Genetics, Jacobsen et al 1 described a screening procedure based on loss of heterozygosity at five microsatellite loci studied by multiplex PCR. For those subjects who were homozygous for the five loci, they conducted further testing with 12 additional microsatellite loci and a methylation sensitive PCR assay (M-PCR) at the SNRPN locus. With this screening approach they examined 285 profoundly retarded adults and detected four cases of AS, a prevalence of 1.4%.

          We have recently completed a study searching for PWS and AS in a group of moderately to severely mentally retarded boys in Brazil. Our screening procedure was based on two tests, the methylation sensitive PCR assay for the α exon in the 5′ region of the SNRPN gene (M-PCR)2 3 and a multiplex PCR involving three of the polymorphic microsatellites in the critical PW/AS region.4For the former, PCR products were separated on non-denaturing polyacrylamide gels stained by silver nitrate,5 while for the latter we used Cy5 labelled primers followed by resolution in an automatic fluorescent DNA sequencer (ALF Express, Pharmacia Biotech). Based on frequencies estimated on normal Brazilian subjects, we would expect that less than 1% of the population would be homozygous for all three microsatellites by chance alone. This double screening procedure was capable of diagnosing with 100% accuracy five patients (three PWS and two AS) known to have chromosomal deletions by FISH (Coriell Cell Repository, Camden, New Jersey, USA) when studied together with DNA samples from 20 normal Brazilians.

          Among mentally retarded boys attending schools for the mentally handicapped in the city of Belo Horizonte, Brazil, 285 without Down syndrome were randomly ascertained. These 256 boys (127 severely retarded and 129 with mild-moderate mental retardation), whose parents gave written permission, were included in the study. School professionals assessed the severity of the mental retardation by applying the Raven scale. All children had been clinically examined by one of us (MJBA). Our results showed that all the boys displayed amplification of both maternal and paternal bands on the M-PCR. Four boys showed a single band at all three microsatellite loci but were considered to be true homozygotes because of a normal M-PCR result and also absence of clinical evidence of PWS or AS on clinical examination. We concluded that none of the 256 patients had PWS or AS.

          Jacobsen et al 1 found a minimum prevalence of 1.4% for AS among severely mentally retarded adults. However, their finding of four affected out of 285 tested is not significantly different from zero by any statistical procedure. Moreover, their study population consisted of severely retarded adults while we studied children with varying degrees of involvement.

          In conclusion, our data are at variance with the claim made by Jacobsenet al 1 of a high prevalence of AS among the mentally retarded. Further studies will have to be undertaken in an effort to assess the true prevalence of PWS and AS among mentally retarded subjects.

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