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Rare Genetic Variation in 135 Families With Family History Suggestive of X-Linked Intellectual Disability.
- Source :
-
Frontiers in genetics [Front Genet] 2019 Jun 26; Vol. 10, pp. 578. Date of Electronic Publication: 2019 Jun 26 (Print Publication: 2019). - Publication Year :
- 2019
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Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 1664-8021
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Frontiers in genetics
- Publication Type :
- Academic Journal
- Accession number :
- 31316545
- Full Text :
- https://doi.org/10.3389/fgene.2019.00578