Somatic mosaicism of a novelIKBKGmutation in a male patient with incontinentia pigmenti
| Autor: | Virginia Hill, Andrew R. Webster, Sarah Hull, Penelope Thomson, Harjeet Rai, Anthony T. Moore, Gavin Arno, Stacey Mutch |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Pathology medicine.medical_specialty Somatic cell Molecular Sequence Data Nonsense mutation Buccal swab Biology IKBKG Genetics medicine Humans Incontinentia Pigmenti Genetics (clinical) Base Sequence medicine.diagnostic_test Mosaicism Genodermatosis Sequence Analysis DNA Incontinentia pigmenti medicine.disease I-kappa B Kinase Germ Cells Phenotype Codon Nonsense Child Preschool Karyotyping Mutation (genetic algorithm) Skin biopsy Immunology Hair |
| Zdroj: | American Journal of Medical Genetics Part A. 167:1601-1604 |
| ISSN: | 1552-4825 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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