title: Critical consequences of finding three pathogenic mutations in an individual with recessive disease.
abstract: 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.
authors.forename: Sally
authors.initials: S
authors.lastname: Halsall
authors.forename: Adeline K
authors.initials: AK
authors.lastname: Nicholas
authors.forename: Gemma
authors.initials: G
authors.lastname: Thornton
authors.forename: Howard
authors.initials: H
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Geoffrey Woods
mesh_terms: D005808:Genes, Recessive; D006801:Humans; D008607:Intellectual Disability / Q000150:complications; D008831:Microcephaly / Q000150:complications / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*
chemical_list: C467202:ASPM protein, human; D009419:Nerve Tissue Proteins