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Homozygosity for autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) does not result in a more severe phenotype
  1. M M O Tonini1,
  2. R C M Pavanello1,
  3. J Gurgel-Giannetti2,
  4. R J Lemmers3,
  5. S M van der Maarel3,
  6. R R Frants3,
  7. M Zatz1
  1. 1Human Genome Research Centre, Departamento de Biologia, Instituto de Biociencias, Universidade de São Paulo, São Paulo, Brazil
  2. 2Division of Neuromuscular Diseases, Hospital das Clínicas, Universidade Federal de Minas Gerais, MG-Brasil
  3. 3Centre for Human and Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
  1. Correspondence to:
 Professor M Zatz
 Centro de Estudos do Genoma Humano, Departamento de Biologia, Instituto de Biociencias, Universidade de São Paulo, São Paulo, 05508-900, Brazil;

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Facioscapulohumeral muscular dystrophy (FSHD) is a relatively common autosomal dominant disorder with an estimated incidence of 1:20 000 births.1 It is clinically characterised by progressive weakness of facial, shoulder girdle, and upper arm muscles; less frequently, the lower limbs are also affected. Some intriguing phenotypic observations are still not understood at the molecular level, such as the existence of clinical anticipation in some multigenerational families, which was observed in several population studies.2–5 In addition, a remarkable inter- and intra-familial clinical variability, ranging from severe infantile forms to asymptomatic or non-penetrant gene carrying, may occur in individuals with an FSHD deleted fragment of the same size. It has been reported that a greater proportion of females than males remain asymptomatic, 1,6 and more recently we have observed that these non-penetrant individuals seem to be concentrated in some families.7

The FSHD1 locus has been mapped to chromosome 4q35, and in most patients the probe p13E-11 detects a polymorphic EcoRI fragment smaller than 35 kb. The size of this fragment ranges from 35 to 300 kb in normal individuals and consists of multiple copies of a tandem repeated 3.3 kb KpnI unit (D4Z4).8 As the 4q35 region is highly homologous to 10q26, the confirmation of molecular diagnosis is performed using BlnI, which cleaves the 10q26 units only into the 3.3 kb fragments, which are undetectable.9 It has been shown that deletions of an integral number of the chromosome 4 units lead to FSHD and that this contraction might affect nearby genes by altering the chromosomal structure, inducing position effect variegation.10

A polymorphic segment distal to D4Z4 with alleles 4qA and 4qB was described by Van Geel et al.11 In a survey in the Dutch population, Lemmers et al12 found …

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