Intellectual disability
Gene: MIR17HG

MIR17HG (miR-17-92a-1 cluster host gene)
EnsemblGeneIds (GRCh38): ENSG00000215417
EnsemblGeneIds (GRCh37): ENSG00000215417
OMIM: 609415, Gene2Phenotype
MIR17HG is in 7 panels

6 reviews

Helen Brittain (Genomics England Curator)

Comment when marking as ready: All cases to date have been CNVs. Need further evidence as to critical region / whether SNVs present in similar manner.
Created: 8 Mar 2018, 2:35 p.m.

Comment on list classification: Sufficient cases associated with copy number losses, however no reported cases to date of SNVs with this phenotype (includes personal correspondence with colleagues undertaking diagnostic testing). The smallest deletion reported encompasses the gene but also includes the first exon of the neighbouring gene, GPC5. Await SNV cases or deletions only including this gene to prompt review.
Created: 8 Mar 2018, 2:34 p.m.

Created: 8 Mar 2018, 2:34 p.m.

Panel version: Imported from Intellectual disability update Jan 2018 panel version 0.453

Louise Daugherty (Genomics England Curator)

Comment on list classification: Promoted gene status from Red to Green, although rare and the phenotype has been extended Feingold syndrome 2, it has been described in six patients worldwide (Sirchia et a.,l (2017) PMID: 28159702. All cases have been described with a form of ID. However no SNV cases in the literature, so needs internal clinical review for confirmation of rating.
Created: 6 Mar 2018, 5:25 p.m.

Comment on publications: Recent papers have gone on to expand the phenotypes of Feingold syndrome-2, illustrating the phenotypic variability within the clinical presentation of Feingold syndrome-2 and highlights considerable overlap with Feingold syndrome-1 but they have all to date included some intellectual disability.

Grote LE et al,. (2015) PMID: 26360630 described a patient that had characteristic digital anomalies and short stature often seen in Feingold syndrome-2 with mild learning difficulties but with with less common features of a congenital heart defect and hearing loss. Additionally, the patient did not have microcephaly.

Sirchia F et al,. (2017) PMID: 28159702 reported 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.
Created: 6 Mar 2018, 5:20 p.m.

Comment on publications: Fiori E, Babicola et al., (2015) PMID: 26026879. Mouse model for Feingold syndrome 2.
Created: 6 Mar 2018, 4:54 p.m.

Comment on publications: Fourth case was described Ganjavi H et al., (2014) PMID: 25391829 in an 18-year-old girl with microcephaly, short stature, mildly dysmorphic features, digital malformations and significant cognitive and psychiatric symptoms. Comparative genomic hybridisation array testing confirmed a 7.4 Mb microdeletion in chromosome region 13q31.1q.31.3 corresponding to the MIR17HG gene.
Created: 6 Mar 2018, 4:44 p.m.

Comment on publications: De Pontual et al. (2011) PMID:21892160 identified three probands with Feingold syndrome type 2. Two female probands were identified via high-resolution CGH arrays identifying germline hemizygous microdeletions at chromosome 13q31.3 that segregated with disease in both families
In additon to this De Pontual et al. (2011) then searched
the DECIPHER database (Firth et al., 2009 PMID:19344873) and they identified a third proband who had a 180-kb hemizygous 13q31.3 microdeletion encompassing the entire MIR17HG gene and the first exon of GPC5. The third patient was not classified as having Feingold syndrome, but displayed a combination of features compatible with the diagnosis.
Created: 6 Mar 2018, 1:57 p.m.

Comment on phenotypes: Added phenotype from OMIM and Orphanet. Feingold syndrome type 2 (FS2) is a rare inherited malformation syndrome characterized by skeletal abnormalities and mild intellectual disabilities similar to those seen in Feingold syndrome type 1 (FS1; see this term) but that lacks the manifestations of gastrointestinal atresia and short palpebral fissures.
Created: 6 Mar 2018, 10:35 a.m.

added tag locus-type-rna-long-non-coding, deletions and watchlist tag
Created: 6 Mar 2018, 10:28 a.m.

Created: 6 Mar 2018, 10:28 a.m.

Panel version: Imported from Intellectual disability update Jan 2018 panel version 0.356

Caroline Wright (Sanger)

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
FEINGOLD SYNDROME

Publications

21892160

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

Ellen McDonagh (Genomics England Curator)

Added tag to explain why there is no Ensembl gene ID for this entity.
Created: 6 Jan 2017, 3:44 p.m.

Created: 6 Jan 2017, 3:44 p.m.

Panel version: 1.23

Lu Raymond (university of cambridge )

I don't know

Created: 23 Feb 2016, 10:17 a.m.

Panel version: 0.306

Richard Scott (Genomics England Curator)

Comment on list classification: Three families with deletions of MIR17HG reported. Requires further data before diagnostic grade
Created: 7 Feb 2016, 11:24 p.m.

Created: 7 Feb 2016, 11:24 p.m.

Panel version: 0.184

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Amber
Expert Review

Phenotypes

Feingold syndrome 2, 614326
FS2
Brachydactyly with short stature and microcephaly
Intellectual disability

Tags

deletions watchlist locus-type-rna-long-non-coding

OMIM

609415

Clinvar variants

Variants in MIR17HG

Penetrance

Complete

Publications

Panels with this gene