Rare Genetic Variation in 135 Families With Family History Suggestive of X-Linked Intellectual Disability
Autor: | Olivera Spasic-Boskovic, F. Lucy Raymond, Christina Bitsara, Keren J. Carss, Joanna Jarvis, Kay Yi Low, Courtney E. French, Alba Sanchis-Juan, Michael Field, Detelina Grozeva |
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Přispěvatelé: | French, Courtney [0000-0001-7620-1544], Raymond, Lucy [0000-0003-2652-3355], Apollo - University of Cambridge Repository |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
lcsh:QH426-470 X-linked intellectual disability Disease Biology 03 medical and health sciences 0302 clinical medicine Intellectual disability Genetic variation autosomal dominant medicine Genetics Family history Genetics (clinical) Phenocopy X-linked Genetic heterogeneity Inheritance (genetic algorithm) Brief Research Report medicine.disease lcsh:Genetics 030104 developmental biology mosaicism intellectual disability 030220 oncology & carcinogenesis Molecular Medicine next-generation sequencing Mendelian disease |
Zdroj: | Frontiers in Genetics Frontiers in Genetics, Vol 10 (2019) |
ISSN: | 1664-8021 |
Popis: | Families with multiple male children with intellectual disability (ID) are usually suspected of having disease due to a X-linked mode of inheritance and genetic studies focus on analysis of segregating variants in X-linked genes. However, the genetic cause of ID remains elusive in approximately 50% of affected individuals. Here, we report the analysis of next-generation sequencing data in 274 affected individuals from 135 families with a family history suggestive of X-linked ID. Genetic diagnoses were obtained for 19% (25/135) of the families, and 24% (33/135) had a variant of uncertain significance. In 12% of cases (16/135), the variants were not shared within the family, suggesting genetic heterogeneity and phenocopies are frequent. Of all the families with reportable variants (43%, 58/135), we observed that 55% (32/58) were in X-linked genes, but 38% (22/58) were in autosomal genes, while the remaining 7% (4/58) had multiple variants in genes with different modes on inheritance. This study highlights that in families with multiple affected males, X linkage should not be assumed, and both individuals should be considered, as different genetic etiologies are common in apparent familial cases. |
Databáze: | OpenAIRE |
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