title: Somatic mosaicism of a novel IKBKG mutation in a male patient with incontinentia pigmenti.
abstract: Incontinentia pigmenti (IP) is an X-linked, dominant genodermatosis usually fatal in utero in males. In rare circumstances, survival is possible due to abnormal karyotype or somatic mosaicism. In this report, the mechanism and significance of loss of detectable mutation in peripheral blood leukocytes of a somatic mosaic male is discussed and an alternative approach to achieving molecular diagnosis presented. A male patient is reported, who initially presented at 2 days of age with a rash and seizure. Clinical assessment and histology of a skin biopsy were consistent with a diagnosis of IP. He was subsequently found to have bilateral retinal detachments. Screening for the common deletion in IKBKG was negative. A novel nonsense variant, c.937C>T (p.Gln313*) in IKBKG was identified at an approximate level of 15% in a blood sample taken at 10 days of age, but was undetectable in a sample taken at 3 years most likely due to selective apoptosis of mutant cells. Samples taken from the patient when he was 5-6 years of age identified the mutation at a low level in hair root and urine but not in blood or buccal cells. The detection of the mutation in cells derived from all germ layers indicates a de novo event at an early stage of embryogenesis. This is the first report of a nonsense mutation in a male IP patient.
authors.affiliation: Inherited Eye Diseases, UCL Institute of Ophthalmology, London, United Kingdom.|Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hull
authors.affiliation: Inherited Eye Diseases, UCL Institute of Ophthalmology, London, United Kingdom.|Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Gavin
authors.initials: G
authors.lastname: Arno
authors.affiliation: Department of Dermatology, Royal Free London NHS Foundation Trust, London, United Kingdom.
authors.forename: Penelope
authors.initials: P
authors.lastname: Thomson
authors.affiliation: East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Stacey
authors.initials: S
authors.lastname: Mutch
authors.affiliation: Inherited Eye Diseases, UCL Institute of Ophthalmology, London, United Kingdom.|Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.affiliation: East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Harjeet
authors.initials: H
authors.lastname: Rai
authors.affiliation: Department of Dermatology, Royal Free London NHS Foundation Trust, London, United Kingdom.
authors.forename: Virginia
authors.initials: V
authors.lastname: Hill
authors.affiliation: Inherited Eye Diseases, UCL Institute of Ophthalmology, London, United Kingdom.|Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics*; D005854:Germ Cells / Q000378:metabolism; D006197:Hair / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics*; D007184:Incontinentia Pigmenti / Q000235:genetics* / Q000473:pathology; D007621:Karyotyping; D008297:Male; D008969:Molecular Sequence Data; D009030:Mosaicism; D010641:Phenotype; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense; C491731:IKBKG protein, human; D051550:I-kappa B Kinase
keywords: apoptosis; incontinentia pigmenti; somatic mosaicism