Year: 2003
Type: dissertation
Study design: Observational Study
Abstract: Background Cleft palate is one of the most common congenital malformations.The incidence of non-syndromic cleft palate only is ~1/1000 live births in Finland.The etiopathogenesis of clefts has been widely studied but is still poorly understood.It has been estimated that about half of the cases are nonsyndromic.Nonsyndromic cleft palate is considered to be a genetically complex, multifactorial disease.The aim of our research was to study genetic component influencing on non-syndromic CPO and Van der Woude syndrome (VWS), which is one of the most common cleft syndromes.We also wanted to study the role of collagens in Robin sequence (RS), which is a triad of cleft palate, micrognathia and glossoptosis.Methods Patients and their families were recruited from the Cleft Center, Helsinki University Hospital.In addition, a few patients were from the USA.Genotyping was done using polymorphic microsatellite markers.Linkage and linkage disequilibrium (LD) between nonsyndromic CPO and candidate regions/genes 1p34, 2q32, 22q11, MSX1 and TGFβ3 were analysed using 24 multiplex families.A genome-wide scan was performed in nine of the largest families with non-syndromic CPO and in one large VWS family unlinked to the previously reported VWS locus in 1q32-q41.COL2A1, COL11A1 and COL11A2 were sequenced in 24 RS patients, 17 CPO patients and 21 patients with micrognathia. ResultsWe found a second locus for VWS in 1p34 that has not previously been reported.Candidate regions/genes did not show any evidence of linkage or LD with non-syndromic CPO.In the genome-wide scan, no significant linkage could be detected, but several interesting regions were found.Two disease-associated mutations were found in COL11A1 and COL11A2 in RS patients.Moreover, two putatively disease-associated mutations were found.Conclusions Candidate regions/genes 2q32, 22q11, MSX1 and TGFβ3 do not play major roles in cleft palate formation in Finnish multiplex families.Failure to detect significant linkage in the genome-wide scan suggests that there might be multiple genes involved in nonsyndromic CPO in Finland.Narrowing down the critical region in 1p34 will be essential in studying the second VWS locus.COL11A1 and COL11A2 have some impact on the Robin sequence but further studies are needed.
Source: Työväentutkimus Vuosikirja
Author: Hannele Koillinen
Language: English
Subfield: Oral Surgery
Field: Dentistry
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W820458540