Targeted carrier screening for four recessive disorders: high detection rate within a founder population

Eur J Med Genet. 2015 Mar;58(3):123-8. doi: 10.1016/j.ejmg.2015.01.004. Epub 2015 Jan 30.


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.

Keywords: Autosomal recessive disorders; Carrier screening; Founder population; Outpatient clinic; Targeted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Arthrogryposis / diagnosis
  • Arthrogryposis / genetics
  • Chondrodysplasia Punctata, Rhizomelic / diagnosis
  • Chondrodysplasia Punctata, Rhizomelic / genetics
  • Female
  • Founder Effect
  • Genes, Recessive*
  • Genetic Carrier Screening / methods*
  • Genetic Counseling
  • Genetic Testing / methods*
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Olivopontocerebellar Atrophies / diagnosis
  • Olivopontocerebellar Atrophies / genetics
  • Osteogenesis Imperfecta / diagnosis
  • Osteogenesis Imperfecta / genetics
  • Pedigree
  • Peroxisomal Targeting Signal 2 Receptor / deficiency
  • Pregnancy
  • Young Adult

Supplementary concepts

  • Pena Shokeir syndrome, type 1
  • Pontocerebellar Hypoplasia Type 2
  • Rhizomelic chondrodysplasia punctata, type 1