title: Familial Pelizaeus-Merzbacher disease caused by a 320.6-kb Xq22.2 duplication and the pathological findings of a male fetus.
abstract: BACKGROUND
  Pelizaeus-Merzbacher disease (PMD) is a recessive, X-linked leukoencephalopathy attributed to impaired myelination during central nervous system development, caused by defects in the proteolipid protein 1 (PLP1) gene. PMD presents clinical variability, ranging from the severe connatal form to the classic form.
  
  
  METHODS
  We report the clinical and molecular findings of two affected males, three carrier females, and an aborted male fetus with familial PMD. The two male probands presented with severe PMD phenotype and intellectual disability. High-resolution oligonucleotide-based array comparative genomic hybridization (aCGH) identified an Xq22.2 duplication of 320.6 kb (102641391-102961998, hg18), including the PLP1 gene and surrounding chromosomal region. Postmortem examination of the aborted fetus at 25 weeks' gestation showed focal subcortical white matter degeneration, focal gliosis, and cerebellar atrophy.
  
  
  CONCLUSIONS
  Genotype-phenotype correlation is provided. In the connatal form of PMD, leukodystrophy and cerebellar atrophy can occur antenatally and be established at 25 weeks' gestation. The observation of degenerative brain lesions occurring before the onset of subcortical myelination suggests that the PLP1 gene has a more complex role in human brain development, exceeding its structural function in myelin formation.
authors.affiliation: Department of Medical Genetics, Medical School, University of Athens, Greece.
authors.forename: Sophia
authors.initials: S
authors.lastname: Kitsiou-Tzeli
authors.forename: Anastasia
authors.initials: A
authors.lastname: Konstantinidou
authors.forename: Christalena
authors.initials: C
authors.lastname: Sofocleous
authors.forename: Konstantina
authors.initials: K
authors.lastname: Kosma
authors.forename: Areti
authors.initials: A
authors.lastname: Syrmou
authors.forename: Krinio
authors.initials: K
authors.lastname: Giannikou
authors.forename: Stavros
authors.initials: S
authors.lastname: Sifakis
authors.forename: Periklis
authors.initials: P
authors.lastname: Makrythanasis
authors.forename: Maria
authors.initials: M
authors.lastname: Tzetis
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002648:Child; D058674:Chromosome Duplication / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D005333:Fetus; D005808:Genes, Recessive; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D010375:Pedigree; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human