VACTERL-like phenotypes

Gene: MIR17HG

Amber List (moderate evidence)

MIR17HG (miR-17-92a-1 cluster host gene)
EnsemblGeneIds (GRCh38): ENSG00000215417
EnsemblGeneIds (GRCh37): ENSG00000215417
OMIM: 609415, Gene2Phenotype
MIR17HG is in 6 panels

4 reviews

Louise Daugherty (Genomics England Curator)

I don't know

Comment on phenotypes: updated to the phenotype to be more descriptive and included the OMIN phenotype
Created: 8 Mar 2018, 3 p.m.
Comment on publications: added publications to support the phenotype
Created: 8 Mar 2018, 2:59 p.m.
Comment on list classification: changed from Red to Amber due to recent update of the ID panel
Created: 8 Mar 2018, 2:58 p.m.
From the ID panel update March 2018.
Helen Brittain (Genomics England Curator), 8 Mar 2018.
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.
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, 2:57 p.m.
From the ID panel update March 2018. Louise Daugherty (Genomics England), 6 Mar 2018.
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.
Comment on publications: Fiori E, Babicola et al., (2015) PMID: 26026879. Mouse model for Feingold syndrome 2.
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.
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.
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.
Comment on list classification: Promoted gene status from Red to Green, although rare and the phenotype has been extended Feingold syndrome 2, been described in six patients worldwide (Sirchia et a.,l (2017) PMID: 28159702. All cases have been described with a form of ID. After Clinical review this was changed to Amber.
Created: 8 Mar 2018, 2:54 p.m.
added tag locus-type-rna-long-non-coding, deletions and watchlist tag
Created: 8 Mar 2018, 2:49 p.m.

Muriel Holder (Clinical Genetics, Guy's Hospital)

Green List (high evidence)

Ellen McDonagh (Genomics England Curator)

Added tag to explain why there is no Ensembl gene ID for this entity.
Created: 6 Jan 2017, 3:43 p.m.

Ellen Thomas (Genomics England Curator)

Comment on list classification: Probably true association, but only deletions reported so far and these include other genes. Await LOF mutations of other types before including on the panel.
Created: 27 May 2016, 11:29 a.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
Phenotypes
  • Feingold syndrome
  • Feingold syndrome 2, 614326
  • FS2
  • Brachydactyly with short stature and microcephaly
Tags
deletions watchlist locus-type-rna-long-non-coding
OMIM
609415
Clinvar variants
Variants in MIR17HG
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

8 Mar 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for MIR17HG were set to Feingold syndrome; Feingold syndrome 2, 614326; FS2; Brachydactyly with short stature and microcephaly

8 Mar 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for MIR17HG were set to 21892160; 19344873; 25391829; 26360630

8 Mar 2018, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

27 May 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen Thomas (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

27 May 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen Thomas (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

16 Nov 2015, Gel status: 0

Added New Source

Muriel Holder (Clinical Genetics, Guy's Hospital)

MIR17HG was added to VACTERL-like phenotypespanel. Sources: Literature

16 Nov 2015, Gel status: 0

Created

Muriel Holder (Clinical Genetics, Guy's Hospital)

MIR17HG was created by mholder