Severe microcephalyGene: DPP6
- 1x proband (OFC < -3 SD) with a missense which segregated in 3 other family members
- 2x probands with 336kb deletion. Both OFCs < -3 SD
- mouse KO model with significantly smaller brain weight
However, note that missense was found using candidate gene approach in a cohort of microcephalic patients. There have been no further reports since 2013. A single LP variant is present in ClinVar but associated with schizophrenia.
Created: 2 Sep 2020, 9:28 p.m. | Last Modified: 2 Sep 2020, 9:28 p.m.
Panel Version: 2.20
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mental retardation, autosomal dominant 33 (MIM#616311)
As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Created: 29 Jul 2019, 4:18 p.m. | Last Modified: 29 Jul 2019, 4:18 p.m.
Panel Version: 1.62
Comment on list classification: Updated rating from Red to Green based on 3 unrelated cases described in PMID:23832105- 2 deletions and a missense.
Created: 2 Mar 2017, 2:55 p.m.
Added 'deletions' tag based on 2 deletions (336 kb and 362 kb) described in PMID:23832105.
Created: 2 Mar 2017, 11:49 a.m.
PMID:23832105 (Liao et al., 2013) identify 2 de novo deletions and 1 missense mutation in familial microcephalic patients.
A 5 year old girl carried the missense (c.1153A-C (NM_130797) transversion, M385L). The same mutation was identified in her affected mother, aunt and grandfather. Patient BY0712 harboured a 336 kb deletion. Patient BY2018 harbored a362 kb deletion.
Created: 27 Feb 2017, 2:44 p.m.
DPP6 is on the Expert list for MCPH (primary microcephaly) from Andrew Jackson but with the caution that only a single mutation or family is reported in the literature.
Created: 13 Dec 2016, 12:11 p.m.
Source NHS GMS was added to DPP6.
2nd March 2017: Panel review was assessed and panel was revised according to expert review and additional curation. This panel began with an expert gene list from Professor Andrew Jackson (University of Edinburgh) for primary microcephaly (MCPH) and microcephalic primordial dwarfism (MPD). Other disorders are included where microcephaly is a primary feature. Disorders where microcephaly is not the primary presenting feature are not included (e.g. congenital disorders of glycosylation, Proud syndrome, Norrie disease). The panel does not include disorders with a cortical malformation (e.g. lissencephaly) since the Malformations of cortical development' panel would be applied to these patients.
This gene has been classified as Green List (High Evidence).
Phenotypes for DPP6 were set to MCPH; primary microcephaly; autosomal dominant microcephaly and mental retardation; Mental retardation, autosomal dominant 33, 616311
Mode of inheritance for DPP6 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for DPP6 were set to 23832105
Phenotypes for DPP6 were set to MCPH; primary microcephaly; autosomal dominant microcephaly and mental retardation
DPP6 was created by rfoulger
DPP6 was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Expert list