We report on a 58-year old woman with microcephaly, mild dysmorphic features, bilateral keratoconus, digital abnormalities, short stature and mild cognitive delay. Except for keratoconus, the phenotype was suggestive for Feingold syndrome type 2 (FGLDS2, MIM 614326), a rare autosomal dominant disorder described in six patients worldwide, due to the haploinsufficiency of MIR17HG, a micro RNA encoding gene. Karyotype showed a de novo deletion on chromosome 13q, further defined by array-Comparative Genomic Hybridization (a-CGH) to a 17.2-Mb region. The deletion included MIR17HG, as expected by the FGLDS2 phenotype, and twelve genes from the keratoconus type 7 locus. Because our patient presented with keratoconus, we propose she further refines disease genes at this locus. Among previously suggested candidates, we exclude DOCK9 and STK24, and propose as best candidates IPO5, DNAJC3, MBNL2 and RAP2A. In conclusion, we report a novel phenotypic association of Feingold syndrome type 2 and keratoconus, a likely contiguous gene syndrome due to a large genomic deletion on 13q spanning MIR17HG and a still to be identified gene for keratoconus.

A case of Feingold type 2 syndrome associated with keratoconus refines keratoconus type 7 locus on chromosome 13q

SIRCHIA, Fabio;DI GREGORIO, ELEONORA;restagno, gabriella;CAVALIERI, Simona;GIORGIO, ELISA;MANCINI, CECILIA;PASINI, Barbara;BRUSCO, Alfredo
2017-01-01

Abstract

We report on a 58-year old woman with microcephaly, mild dysmorphic features, bilateral keratoconus, digital abnormalities, short stature and mild cognitive delay. Except for keratoconus, the phenotype was suggestive for Feingold syndrome type 2 (FGLDS2, MIM 614326), a rare autosomal dominant disorder described in six patients worldwide, due to the haploinsufficiency of MIR17HG, a micro RNA encoding gene. Karyotype showed a de novo deletion on chromosome 13q, further defined by array-Comparative Genomic Hybridization (a-CGH) to a 17.2-Mb region. The deletion included MIR17HG, as expected by the FGLDS2 phenotype, and twelve genes from the keratoconus type 7 locus. Because our patient presented with keratoconus, we propose she further refines disease genes at this locus. Among previously suggested candidates, we exclude DOCK9 and STK24, and propose as best candidates IPO5, DNAJC3, MBNL2 and RAP2A. In conclusion, we report a novel phenotypic association of Feingold syndrome type 2 and keratoconus, a likely contiguous gene syndrome due to a large genomic deletion on 13q spanning MIR17HG and a still to be identified gene for keratoconus.
2017
60
4
224
227
http://www.elsevier.com/wps/find/journaldescription.cws_home/705239/description#description
Array-CGH, Feingold syndrome, IPO5, Keratoconus, MBNL2, MIR17HG, SLITRK1, Genetics
Sirchia, Fabio; Di Gregorio, Eleonora; Restagno, Gabriella; Grosso, Enrico; Pappi, Patrizia; Talarico, Flavia; Savin, Elisa; Cavalieri, Simona; Giorgi...espandi
File in questo prodotto:
File Dimensione Formato  
111.Keratoconus and Feingold .pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 578.4 kB
Formato Adobe PDF
578.4 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Feingold_joined_4aperto.pdf

Accesso aperto

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 1.92 MB
Formato Adobe PDF
1.92 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1627472
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 10
social impact