title: Targeted carrier screening for four recessive disorders: high detection rate within a founder population.
abstract: In a genetically isolated community in the Netherlands four severe recessive genetic disorders occur at relatively high frequency (pontocerebellar hypoplasia type 2 (PCH2), fetal akinesia deformation sequence (FADS), rhizomelic chondrodysplasia punctata type 1 (RCDP1), and osteogenesis imperfecta (OI) type IIB/III. Over the past decades multiple patients with these disorders have been identified. This warranted the start of a preconception outpatient clinic, in 2012, aimed at couples planning a pregnancy. The aim of our study was to evaluate the offer of targeted genetic carrier screening as a method to identify high-risk couples for having affected offspring in this high-risk subpopulation. In one year, 203 individuals (92 couples and 19 individuals) were counseled. In total, 65 of 196 (33.2%) tested individuals were carriers of at least one disease, five (7.7%) of them being carriers of two diseases. Carrier frequencies of PCH2, FADS, RCDP1, and OI were 14.3%, 11.2%, 6.1%, and 4.1% respectively. In individuals with a positive family history for one of the diseases, the carrier frequency was 57.8%; for those with a negative family history this was 25.8%. Four PCH2 carrier-couples were identified. Thus, targeted (preconception) carrier screening in this genetically isolated population in which a high prevalence of specific disorders occurs detects a high number of carriers, and is likely to be more effective compared to cascade genetic testing. Our findings and set-up can be seen as a model for carrier screening in other high-risk subpopulations and contributes to the discussion about the way carrier screening can be offered and organized in the general population.
authors: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: i.b.mathijssen@amc.uva.nl.
authors: Inge B
authors: IB
authors: Mathijssen
authors: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors: Lidewij
authors: L
authors: Henneman
authors: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors: Janneke M C
authors: JM
authors: van Eeten-Nijman
authors: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors: Phillis
authors: P
authors: Lakeman
authors: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors: Cecile P E
authors: CP
authors: Ottenheim
authors: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors: Egbert J W
authors: EJ
authors: Redeker
authors: Waterland Oost Midwifery Practice, Volendam, The Netherlands.
authors: Winnie
authors: W
authors: Ottenhof
authors: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands; Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors: Hanne
authors: H
authors: Meijers-Heijboer
authors: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors: Merel C
authors: MC
authors: van Maarle
mesh_terms: D000293:Adolescent; D000328:Adult; D001176:Arthrogryposis / Q000175:diagnosis / Q000235:genetics; D018902:Chondrodysplasia Punctata, Rhizomelic / Q000175:diagnosis / Q000235:genetics; D005260:Female; D018703:Founder Effect; D005808:Genes, Recessive; D006580:Genetic Carrier Screening / Q000379:methods*; D005817:Genetic Counseling; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009849:Olivopontocerebellar Atrophies / Q000175:diagnosis / Q000235:genetics; D010013:Osteogenesis Imperfecta / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree; D000074437:Peroxisomal Targeting Signal 2 Receptor / Q000172:deficiency; D011247:Pregnancy; D055815:Young Adult
keywords: Autosomal recessive disorders; Carrier screening; Founder population; Outpatient clinic; Targeted