A case of Feingold type 2 syndrome associated with keratoconus refines keratoconus type 7 locus on chromosome 13q.
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.
Città Della Salute e Della Scienza University Hospital, Medical Genetics Unit, Turin, 10126 Italy.
Fabio
F
Sirchia
Città Della Salute e Della Scienza University Hospital, Medical Genetics Unit, Turin, 10126 Italy; University of Torino, Department of Medical Sciences, Turin, 10126, Italy.
Eleonora
E
Di Gregorio
Città Della Salute e Della Scienza University Hospital, Medical Genetics Unit, Turin, 10126 Italy.
Gabriella
G
Restagno
Città Della Salute e Della Scienza University Hospital, Medical Genetics Unit, Turin, 10126 Italy.
Enrico
E
Grosso
Città Della Salute e Della Scienza University Hospital, Medical Genetics Unit, Turin, 10126 Italy.
Patrizia
P
Pappi
Città Della Salute e Della Scienza University Hospital, Medical Genetics Unit, Turin, 10126 Italy.
Flavia
F
Talarico
Città Della Salute e Della Scienza University Hospital, Medical Genetics Unit, Turin, 10126 Italy.
Elisa
E
Savin
Città Della Salute e Della Scienza University Hospital, Medical Genetics Unit, Turin, 10126 Italy.
Simona
S
Cavalieri
University of Torino, Department of Medical Sciences, Turin, 10126, Italy.
Elisa
E
Giorgio
University of Torino, Department of Medical Sciences, Turin, 10126, Italy.
Cecilia
C
Mancini
Città Della Salute e Della Scienza University Hospital, Medical Genetics Unit, Turin, 10126 Italy; University of Torino, Department of Medical Sciences, Turin, 10126, Italy.
Barbara
B
Pasini
Singapore National Eye Centre & Duke-NUS Graduate Medical School, Singapore, Singapore.
Jodhbir S
JS
Mehta
Città Della Salute e Della Scienza University Hospital, Medical Genetics Unit, Turin, 10126 Italy; University of Torino, Department of Medical Sciences, Turin, 10126, Italy. Electronic address: alfredo.brusco@unito.it.
Alfredo
A
Brusco
D000015:Abnormalities, Multiple; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D055028:Comparative Genomic Hybridization; D003582:Cytogenetics; D005143:Eyelids / Q000002:abnormalities*; D005260:Female; D017353:Gene Deletion; D057895:Haploinsufficiency; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D007621:Karyotyping; D007640:Keratoconus / Q000150:complications / Q000235:genetics*; D017880:Limb Deformities, Congenital / Q000150:complications / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000150:complications / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D014138:Tracheoesophageal Fistula / Q000150:complications / Q000235:genetics*
Array-CGH; Feingold syndrome; IPO5; Keratoconus; MBNL2; MIR17HG; SLITRK1