Details

Autor(en) / Beteiligte

• Balci, T.B.
• Hartley, T.
• Xi, Y.
• Dyment, D.A.
• Beaulieu, C.L.
• Bernier, F.P.
• Dupuis, L.
• Horvath, G.A.
• Mendoza‐Londono, R.
• Prasad, C.
• Richer, J.
• Yang, X.‐R.
• Armour, C.M.
• Bareke, E.
• Fernandez, B.A.
• McMillan, H.J.
• Lamont, R.E.
• Majewski, J.
• Parboosingh, J.S.
• Prasad, A.N.
• Rupar, C.A.
• Schwartzentruber, J.
• Smith, A.C.
• Tétreault, M.
• Innes, A.M.
• Boycott, K.M.

Titel

Debunking Occam's razor: Diagnosing multiple genetic diseases in families by whole‐exome sequencing

Ist Teil von

• Clinical genetics, 2017-09, Vol.92 (3), p.281-289

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2017

Quelle

Wiley Online Library Journals【Remote access available】

Beschreibungen/Notizen

• Background Recent clinical whole exome sequencing (WES) cohorts have identified unanticipated multiple genetic diagnoses in single patients. However, the frequency of multiple genetic diagnoses in families is largely unknown. Aims We set out to identify the rate of multiple genetic diagnoses in probands and their families referred for analysis in two national research programs in Canada. Materials & Methods We retrospectively analyzed WES results for 802 undiagnosed probands referred over the past 5 years in either the FORGE or Care4Rare Canada WES initiatives. Results Of the 802 probands, 226 (28.2%) were diagnosed based on mutations in known disease genes. Eight (3.5%) had two or more genetic diagnoses explaining their clinical phenotype, a rate in keeping with the large published studies (average 4.3%; 1.4 ‐ 7.2%). Seven of the 8 probands had family members with one or more of the molecularly diagnosed diseases. Consanguinity and multisystem disease appeared to increase the likelihood of multiple genetic diagnoses in a family. Conclusion Our findings highlight the importance of comprehensive clinical phenotyping of family members to ultimately provide accurate genetic counseling.