Intellectual disability update Jan 2018

Gene: MED25

Comment when marking as ready: It is interesting as both populations studied are highly consanguineous and aside from ID, the phenotype is not clearly the same. The facial features are not clearly in keeping (although the images shown are from very different points in life and coarsening over time could be envisaged). Also, one cohort had ocular features whereas the other doesn't. Further cases are needed, preferably from alternative backgrounds to inform about causation and the associated core phenotype. Amber and watchlist is appropriate.

Created: 8 Mar 2018, 3:04 p.m.

watchlist and founder-effect tags added

Created: 8 Mar 2018, 3:52 p.m.

Comment on list classification: changed from Red to Amber- for clinical review. Possible founder effect but also consideration of two papers describe families from two distinct regions Palestine and Northeastern Brazil. All cases with a form of ID.

Created: 7 Mar 2018, 5:14 p.m.

Comment on publications: In the same year Figueiredo T et al,. (2015) PMID: 25527630 found a homozygous missense p.(Arg140Trp) mutation in MED25 in a large consanguineous family from Northeastern Brazil in which seven adults were diagnosed with syndromic intellectual disability.

Created: 7 Mar 2018, 4:58 p.m.

Comment on publications: Basel-Vanagaite et al. (2015) PMID: 25792360 reported 7 children from 4 unrelated families living in the same small village in Israel with a severe syndromic neurodevelopmental disorder. All had severely delayed psychomotor development apparent from infancy and variable eye abnormalities, including ptosis, microcornea, and congenital cataracts. None of the children was able to speak or walk independently, including the oldest, who was 13 years old. The study showed that a homozygous mutation p.(Tyr39Cys)in MED25 was responsible for a previously undescribed syndrome characterized by severe intellectual disability, characteristic dysmorphic features, congenital eye abnormalities, corpus callosum abnormalities and other congenital abnormalities. They identified a carrier rate of 8.7 % among the inhabitants of the village from which all the families described in this study originated. The high prevalence of the mutation can be explained both by the founder effect owing to the generally high consanguinity rate among the inhabitants of the village, and also because several families in this village had excessive numbers of intellectually disabled offspring due to founder mutations of other genes related to intellectual disability.

Created: 7 Mar 2018, 4:55 p.m.

Comment on phenotypes: added relevant phenotype from OMIM, Orphanet and PMID:25527630

Created: 7 Mar 2018, 3:08 p.m.