RT Journal Article
SR Electronic
T1 Critical consequences of finding three pathogenic mutations in an individual with recessive disease
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 769
OP 770
DO 10.1136/jmg.2010.079277
VO 47
IS 11
A1 Sally Halsall
A1 Adeline K Nicholas
A1 Gemma Thornton
A1 Howard Martin
A1 C Geoffrey Woods
YR 2010
UL http://jmg.bmj.com/content/47/11/769.abstract
AB The authors report the unexpected finding of three different nonsense mutations in two unrelated individuals with a diagnosis of autosomal recessive primary microcephaly. In each case one phenotypically normal parent was found to carry two of the nonsense mutations, presumably in cis. This finding of ‘triple pathogenic mutations’ is of unknown incidence but has significant implication for genetic counselling. A failure to detect all three mutations could result in both false positive and false negative diagnoses in other family members. Both of these potential problems can be avoided by always genotyping the parents.