Skeletal dysplasia

Gene: MIR17HG

Red List (low evidence)

Hand and foot abnormalities may include hypoplastic thumbs, clinodactyly of second and fifth fingers, syndactyly (characteristically between second and third and fourth and fifth toes), and shortened or absent middle phalanges. Microdeletions of 13q31.3 in 2 families. Third case with overlapping clinical features. No case with variants in gene or deletion that only includes this gene.; Review on behalf of Tracy Lester

Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Feingold syndrome 2, 614326

Publications

• 21892160
• 25391829
• 19344873
• 26360630

I don't know

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: MIR17HG; Initial rating suggestion: green for CNVs, red for gene

Created: 6 Mar 2019, 11:36 a.m.

I don't know

Comment on list classification: changed from Green to Amber due to recent update of the ID panel.

Created: 8 Mar 2018, 3:11 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, 3:10 p.m.

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, 3:10 p.m.

added tag locus-type-rna-long-non-coding, deletions and watchlist tag

Created: 8 Mar 2018, 3:09 p.m.

Comment on publications: added more publications to support to the phenotype

Created: 8 Mar 2018, 3:08 p.m.

Comment on phenotypes: amended phenotype due to review/expert review

Created: 6 Mar 2018, 10:30 a.m.

Added tag to explain why there is no Ensembl gene ID for this entity.

Created: 6 Jan 2017, 3:45 p.m.

Comment when marking as ready: Associated with phenotype in OMIM and G2P. At least four deletion variants reported encompassing all or part of this gene

Created: 29 Jul 2016, 7:38 a.m.

Green List (high evidence)

Tier 2

Created: 17 Jun 2016, 8:06 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Feingold syndrome 2 (Microcephaly-oculo-digito-esophageal-duodenal syndrome) 614326

Variants in this GENE are reported as part of current diagnostic practice