Cryptic 7q21 and 9p23 deletions in a patient with apparently balanced de novo reciprocal translocation t(7;9)(q21;p23) associated with a dystonia-plus syndrome: paternal deletion of the epsilon-sarcoglycan (SGCE) gene

J Hum Genet. 2008;53(10):876-885. doi: 10.1007/s10038-008-0321-z. Epub 2008 Jul 24.

Abstract

We report on a boy with myoclonus-dystonia (M-D), language delay, and malformative anomalies. Genetic investigations allowed the identification of an apparently balanced de novo reciprocal translocation, t(7;9)(q21;p23). Breakpoint-region mapping using fluorescent in situ hybridization (FISH) analysis of bacterial artificial chromosome (BAC) clone probes identified microdeletions of 3.7 and 5.2 Mb within 7q21 and 9p23 breakpoint regions, respectively. Genotyping with microsatellite markers showed that deletions originated from paternal alleles. The deleted region on chromosome 7q21 includes a large imprinted gene cluster. SGCE and PEG10 are two maternally imprinted genes. SGCE mutations are implicated in M-D. In our case, M-D is due to deletion of the paternal allele of the SGCE gene. PEG10 is strongly expressed in the placenta and is essential for embryo development. Prenatal growth retardation identified in the patient may be due to deletion of the paternal allele of the PEG10 gene. Other genes in the deleted region on chromosome 7 are not imprinted. Nevertheless, a phenotype can be due to haploinsufficiency of these genes. KRIT1 is implicated in familial forms of cerebral cavernous malformations, and COL1A2 may be implicated in very mild forms of osteogenesis imperfecta. The deleted region on chromosome 9 overlaps with the candidate region for monosomy 9p syndrome. The proband shows dysmorphic features compatible with monosomy 9p syndrome, without mental impairment. These results emphasize that the phenotypic abnormalities of apparently balanced de novo translocations can be due to cryptic deletions and that the precise mapping of these aneusomies may improve clinical management.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Banding
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 7 / genetics*
  • Chromosomes, Human, Pair 9 / genetics*
  • Developmental Disabilities
  • Dystonic Disorders / diagnosis
  • Dystonic Disorders / genetics*
  • Fathers
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Male
  • Myoclonus / diagnosis
  • Myoclonus / genetics*
  • Sarcoglycans / genetics*
  • Syndrome
  • Translocation, Genetic / genetics*

Substances

  • SGCE protein, human
  • Sarcoglycans