Severe microcephaly

Gene: MIR17HG

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.

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.

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
FEINGOLD SYNDROME

Publications

• 21892160

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

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

I don't know

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.