Mild ring 17 syndrome shares common phenotypic features irrespective of the chromosomal breakpoints location

C. Surace, S. Piazzolla, P. Sirleto, M. C. Digilio, M. C. Roberti, A. Lombardo, G. D'Elia, A. C. Tomaiuolo, S. Petrocchi, R. Capolino, M. El Hachem, D. Claps Sepulveda, A. Sgura, A. Angioni

Research output: Contribution to journalArticlepeer-review

Abstract

Surace C, Piazzolla S, Sirleto P, Digilio MC, Roberti MC, Lombardo A, D'Elia G, Tomaiuolo AC, Petrocchi S, Capolino R, El Hachem M, Claps Sepulveda D, Sgura A Angioni A. Mild ring 17 syndrome shares common phenotypic features irrespective of the chromosomal breakpoints location. Ring 17 syndrome is a rare disorder with clinical features influenced by the presence or deletion of the Miller-Dieker critical region (MDCR). Presence of the MDCR is associated with a mild phenotype, including growth delay (GD), mental retardation (MR), seizures, cafè au lait skin (CALS) spots and minor facial dysmorphisms. Previous studies have been mainly focused on this locus providing poor information about the role of other genes located on the p- and q-arms. Here, we used bacterial artificial chromosome (BAC)/P1 artificial chromosome (PAC) and fosmid clones as fluorescence in situ hybridization (FISH) probes to perform a cyto-molecular analysis of a ring 17 case and found that the breakpoints were close to the telomeric ends. METRNL is the sole gene located on the q-arm terminal end, whereas two open reading frames and the RPH3AL gene are located on the terminal p-arm. To detect possibly unrevealed small deletions involving the transcription units, we used subcloned FISH probes obtained by long-range polymerase chain reaction (PCR), which showed that the investigated regions were preserved. Comparing our findings with other reports, it emerges that different breakpoints, involving (or not) large genomic deletions, present overlapping clinical aspects. In conclusion, our data suggest that a mechanism based on gene expression control besides haploinsufficiency should be considered to explain the common phenotypic features found in the mild ring 17 syndrome.

Original languageEnglish
Pages (from-to)256-262
Number of pages7
JournalClinical Genetics
Volume76
Issue number3
DOIs
Publication statusPublished - Sep 2009

Keywords

  • $Fish$Metrnl$Ring$Rph3al$Telomere position effect
  • Fish
  • Metrnl
  • Ring
  • Rph3al
  • Telomere position effect

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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