Table 1.
Founder mutations in different Dutch genetically isolated communities and the coverage of these mutations in expanded carrier screening tests
| Disorder | OMIM | Disease severitya | Gene | Mutation | Populationb | Carrier frequency genetic isolatec | Carrier frequency Dutch general populationd | Counsyle | GenPath Diagnosticsf | Mount Sinaig | Pathway Genomicsh | Recombinei | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fetal akinesia deformation sequence (FADS) | 208150 | 4 | MUSK | c.1724T>C p.(Ile575Thr) | 1 | 8.1–11.2% | <0.2% | − | − | − | − | − | Mathijssen et al. (2015) and Tan-Sindhunata et al. (2015) |
| Osteogenesis imperfecta type IIB/III (OI) | 610682 | 3 | CRTAP | c.21_22dupGG p.(Ala8fs) | 1 | 4.1% | <0.2% | − | − | − | − | − | Mathijssen et al. (2015) and van Dijk et al. (2009) |
| Phenylketonuria (PKU) | 261600 | 3 | PAH | c.1315+1G>A | 1 | 9.2% | <0.2% | + | + | + | –j | + | Oorthuys et al. (1985) |
| Pontocerebellar hypoplasia type 2 (PCH2) | 277470 | 4 | TSEN54 | c.919G>T p.(Ala307Ser) | 1 | 1.5–14.3% | 0.8% | − | − | − | − | + | Barth et al. (1990), Budde et al. (2008), and Mathijssen et al. (2015) |
| Primary ciliary dyskinesia (PCD) | 615067 | 2 | CCDC114 | c.742G>A p.(Gly248Thrfs) | 1 | 10% | 0.4% | − | − | − | − | − | Onoufriadis et al. (2013) |
| Pseudoxanthoma elasticum (PXE) | 264800 | 3 | ABCC6 | c.3775delT p.(Trp1259Glyfs) | 1 | 15 cases described (~21,500) | 0.8% | − | –j | − | − | − | Bergen et al. (2000) and Plomp et al. (2009) |
| Retinitis pigmentosa type 12 (RP12) | 600105 | 2 | CRB1 | c.3122T>C p.(Met1041Thr) | 1 | 4.1% | <0.2% | − | –j | + | − | − | Den Hollander et al. (1999) and Mathijssen et al. (2017) |
| Rhizomelic chondrodysplasia punctata type 1 (RCDP1) | 215100 | 4 | PEX7 | c.875T>A p.(Leu292X) | 1 | 6.1% | <0.2% | + | + | + | − | + | Mathijssen et al. (2015) |
| Van Buchem disease (VBCH) | 239100 | 3 | SOST | 52 kb deletion approximately 35 kb downstream of gene | 2 | ≥13 cases described (~20,000) | <0.2% | − | − | − | − | − | Balemans et al. (2002) and Van Buchem et al. (1955) |
| Congenital retinal dystrophy | 204100 | 2 | RPE65 | c.1102T>C p.(Tyr368His) | 2 | 3.1–7.7% | 0.4% | − | − | + | − | + | Schappert-Kimmijser et al. (1959) and Yzer et al. (2003) |
| Retinitis punctata albescens (RPA) | 136880 | 2 | LRAT | c.12delC p.(Met5CysfsX53) | 2 | 4 cases described (~20,000) | <0.2% | − | − | − | − | − | Littink et al. (2012) |
| Vici syndrome (variant form) | 242840 | 4 | EPG5 | c.4862G>A p.(Arg1621Gln) | 2 | ±10% (pc) | <0.2% | − | − | − | − | − | |
| Benign recurrent intrahepatic cholestasis (BRIC) | 243300 | 2 | ATP8B1 | c.2932-3C>A, skipping of exon 24 | 3 | ≥7 cases described (~20,000) | <0.2% | − | − | − | − | − | De Koning et al. (1995), Houwen et al. (1994) and Klomp et al. (2004) |
| Chudley-McCullough syndrome (CMCS) | 604213 | 2 | GPSM2 | c.1473delG p.(Phe492SerfsX5) | 4 | 3 cases described (~15,000) | <0.2% | − | − | − | − | − | Almomani et al. (2013) and Hendriks et al. (1999) |
| Juvenile neuronal ceroid lipofuscinosis (CLN3) | 204200 | 4 | CLN3 | 1.02 kb deletion | 5 | 17 cases described | 0.5% | + | − | + | − | − | Taschner et al. (1995) |
| Parkinson disease type 7 (PARK7) | 606324 | 3 | DJ-1 | 14 kb deletion | 6 | 0.9% | <0.2% | − | − | − | − | − | Bonifati et al. (2003) |
“+” presence of the mutation in panel. “−” absence of the mutation in panel, pc personal communications
aDisease severity; 1 = mild, 2 = moderate, 3 = severe, 4 = profound (Lazarin et al. 2014). Scored independently by IM and IK. Discrepancies were discussed until consensus was reached
bSix different Dutch founder populations (coded from 1 to 6)
cIf the carrier frequency in the genetically isolated community is not known, the number of cases described in the literature and the current population size of the genetically isolated community is noted
dDerived from Genome of the Netherlands (GoNL) project, http://www.nlgenome.nl; accessed 23 February 2017
eFamily Prep Screen (113 disorders); https://www.counsyl.com/services/family-prep-screen; accessed 6 February 2017
fInheriGen Plus (167 disorders); http://www.genpathdiagnostics.com/womens-health/inherigen; accessed 6 February 2017
gNextStep Pan-Ethnic Carrier Screen (281 disorders); http://nextsteptest.com; accessed 6 February 2017
hCarrier Status DNA Insight (72 disorders); https://www.pathway.com/carrier-status-dna-insight; accessed 6 February 2017
iCarrierMap (315 disorders); http://www.recombine.com/carriermap; accessed 6 February 2017
jA selection of mutations is included in the carrier screening, but the founder mutation is not