Clefting
Gene: MED25The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 4:45 p.m. | Last Modified: 3 Mar 2022, 4:45 p.m.
Panel Version: 2.63
Comment on list classification: Leaving the rating as Amber for now, but there are sufficient cases with clefting to promote this gene to green on this panel after the next GMS review.Created: 9 Dec 2020, 12:38 p.m. | Last Modified: 9 Dec 2020, 12:38 p.m.
Panel Version: 2.9
Additional publications:
Reports with cleft palate reported:
PMID: 31602195 Nair et al 2019 - report a Lebanese family with 2 affected siblings. They presented with severely delayed psychomotor and language development as well as craniofacial anomalies. In 1 sibling cleft palate was noted at birth. Using WES, a homozygous variant was found in MED25 (c.518T>C, p.Ile173Thr) in both siblings. The variant was found in the gnomAD database at a very low frequency (0.00003470) and only in heterozygous state.
PMID: 32324310 - Haynes et al 2020 - report 3 unrelated cases, all presenting with cleft palate among other features such as severe/profound intellectual disability, ocular abnormalities and seizures. 2 patients had homozygous variants in MED25 and the other was compound heterozygous for two variants in MED25. They classified the variants as VUS.
PMID: 32816121 - Maini et al 2020 - report 2 siblings with consanguineous parents presenting with intellectual disability, neurological findings, and dysmorphic features typical of BVSYS, and also with bilateral perisylvian polymicrogyria. Cleft palate was reported in 1 sister. Using WES the identified a homozygous frameshift variant in the MED25:NM_030973.3:c.1778_1779delAG, p.(Gln593Argfs).
Reports with no cleft palate reported:
PMID: 25527630 - Figueiredo et al 2015 - report a consanguineous Brazilian family in which seven adults presented syndromic ID. By linkage analysis and WES they found a homozygous MED25 c.418C>T, arg140-to-trp variant that segregated with the disorder. Cleft palate was NOT reported.
PMID: 30800049 - Nair et al 2019 - Lebanese patient with first cousin parents, and severe neurodevelopmental delay, seizures, ataxia, absence of speech, intellectual disability, stereotypic hand movements, and microcephaly but NO cleft palate. Two homozygous variants were found through WES, COQ8A (ADCK3) c.1534C>T (p.Arg512Trp) and MED25:c.518T>C; p.Ile173Thr. Both very rare in the gnomad database.
22 individuals in total so far who have Basel-Vanagaite-Smirin-Yosef Syndrome. 7 out of 22 individuals (from 6 families (treating the families in PMID: 25792360 as related) present with cleft palate.Created: 9 Dec 2020, 12:36 p.m. | Last Modified: 9 Dec 2020, 12:36 p.m.
Panel Version: 2.8
Phenotypes
Basel-Vanagait-Smirin-Yosef syndrome OMIM:616449
Publications
added founder effect tagCreated: 8 Mar 2018, 3:56 p.m.
4 families but all from the same village with the same mutation. Further evidence considered necessary re causationCreated: 26 May 2017, 7:40 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
BASEL-VANAGAITE-SMIRIN-YOSEF SYNDROME; BVSYS
Publications
Tag for-review was removed from gene: MED25.
Source Expert Review Green was added to MED25. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: MED25 were changed from BASEL-VANAGAITE-SMIRIN-YOSEF SYNDROME; BVSYS to Basel-Vanagait-Smirin-Yosef syndrome OMIM:616449
Publications for gene: MED25 were set to 25792360
Gene: med25 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: MED25.
Panel reviews were assessed, and panel was revised according to reviews and further curation 31st May 2017
MED25 was created by ellenmcdonagh
MED25 was added to Cleftingpanel. Sources: Expert Review Amber