Three brothers with a nonsense mutation in KAT6A caused by parental germline mosaicism
| Autor: | Koh-ichiro Yoshiura, Ryuta Maekawa, Chisei Satoh, Haruo Takahashi, Mutsuko Miyazaki, Tatsuro Kondoh, Hiroyuki Mishima, Akira Kinoshita, Michiko Doi, Masafumi Fukuda |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetics Genetic counselling business.industry Genetic counseling Neurodevelopmental disorders Nonsense mutation Germline mosaicism Biochemistry Article 03 medical and health sciences 030104 developmental biology Germline mutation Mutation Speech delay Mutation (genetic algorithm) medicine Global developmental delay medicine.symptom Sibling business Molecular Biology |
| Zdroj: | Human Genome Variation |
| ISSN: | 2054-345X |
| Popis: | Mutations in KAT6A, encoding a member of the MYST family of histone acetyl-transferases, were recently reported in patients with a neurodevelopmental disorder (OMIM: #616268, autosomal dominant mental retardation-32). In this report, we describe three siblings with intellectual disability (ID) or global developmental delay and a KAT6A heterozygous nonsense mutation, i.e., c.3070C>T (p.R1024*, ENST00000406337; chr8:41795056G>A on hg19). This mutation was identified by whole-exome sequencing of all three siblings but not in a healthy sibling. The mutation was not detected in the peripheral blood of their parents, suggesting the existence of parental germline mosaicism. The primary symptoms of our patients included severe to profound ID or global developmental delay, including speech delay with craniofacial dysmorphism; these symptoms are consistent with symptoms previously described for patients with KAT6A mutations. Although several features are common among patients with KAT6A mutations, the features are relatively nonspecific, making it difficult to establish a clinical entity based on clinical findings alone. To the best of our knowledge, this is the first report of cases with a KAT6A mutation in an Asian population and these cases represent the first reported instances of germline mosaicism of this disease. Intellectual disability: Novel inheritance of mutation A rare intellectual disability can be inherited from a mutation found in a parent’s reproductive cells but not other body cells. Koh-ichiro Yoshiura of Nagasaki University and colleagues in Japan analyzed the genes of a family with three siblings affected by intellectual disability. Peripheral blood samples showed the KAT6A gene was mutated in the affected children but not in their healthy sibling or parents. The similar clinical presentations of the affected children suggests inheritance. Absence of the mutation in the parent’s blood indicates it came from a parent whose reproductive or ‘germ’ cells have a different genetic makeup from their body cells, known as ‘germline mosacism’. This is the first reported case of inheritance of this mutation from germline mosaicism and has implications for genetic counseling. |
| Databáze: | OpenAIRE |
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