De ontwikkeling van de hersenschors is een complex proces, dat strikt gereguleerd is in tijd en ruimte. Zeldzame genetische mutaties die dit proces beïnvloeden, kunnen ingrijpende gevolgen hebben op de intellectuele ontwikkeling, motorische vaardigheden zoals spraak en lopen, gedrag en epilpesie. We focussen specifiek op misvormingen van de hersenschors, geclassificeerd op radiologisch (MRI) scans, zoals lissencefalie, nodulaire heterotopie, polymicrogyrie, microcefalie, megalencefalie, schizencefalie en porencefalie. Deze zijn allemaal zeldzaam en er is zeer weinig bekend over de oorzaak en ziektemechanismen. We streven ernaar nieuwe genen en ziektemechanismen te ontdekken.
Het onderzoek naar corticale malformaties wordt uitgevoerd op de afdeling Klinische Genetica (Mancini lab) en is primair gericht op de identificatie van de genen die corticale malformatie veroorzaken. Daarvoor wordt opgeslagen materiaal van niet-gediagnosticeerde patiënten gebruikt om nieuwe kandidaatgenen te identificeren met WES/WGS, RNAseq en functionele biochemische testen op (stam)cellen. De focus ligt op specifieke mechanismen die betrokken zijn bij de ontwikkeling van de hersenen, zoals regulatie van cel-cel interactie (bv. Vorming en functie van primaire cilia en celmigratie), celproliferatie (regulatie van mitose) en regulatie van celdood (apoptose). We gebruiken niet alleen cellulaire modellen maar ook zebravissen om de rol van deze genen te onderzoeken. Brede nationale en internationale samenwerkingen maken bevestiging en validatie bij extra personen mogelijk.
Tot op heden hebben we hersenmisvormingen ontdekt die worden veroorzaakt door mutaties in de volgende genen: AP4M1, IER3IP1, RTTN, COL4A2, USP18, MOCS3, INTS1, INTS8, MACF1, CARS, SMPD4, TMX2. De Mancini-groep heeft ook meegewerkt aan de karakterisering van hersenmisvormingen en van menselijke mutaties in de volgende genen: ACTB, PIK3CA, AKT3, CCND2, SCN3A, APC2, EML1, ISPD, CSTB, PNKP, ZIC1.
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