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Am J Med Genet A. 2018 Jun;176(6):1315-1326. doi: 10.1002/ajmg.a.38699. Epub 2018 Apr 25.

The phenotypic spectrum of Xia-Gibbs syndrome.

Author information

1
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
2
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
3
Texas Children's Hospital, Houston, Texas.
4
Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, Texas.
5
Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
6
Medical Research Council Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, United Kingdom.

Abstract

Xia-Gibbs syndrome (XGS: OMIM # 615829) results from de novo truncating mutations within the AT-Hook DNA Binding Motif Containing 1 gene (AHDC1). To further define the phenotypic and molecular spectrum of this disorder, we established an XGS Registry and recruited patients from a worldwide pool of approximately 60 probands. Additional de novo truncating mutations were observed among 25 individuals, extending both the known number of mutation sites and the range of positions within the coding region that were sensitive to alteration. Detailed phenotypic examination of 20 of these patients via clinical records review and data collection from additional surveys showed a wider age range than previously described. Data from developmental milestones showed evidence for delayed speech and that males were more severely affected. Neuroimaging from six available patients showed an associated thinning of the corpus callosum and posterior fossa cysts. An increased risk of both scoliosis and seizures relative to the population burden was also observed. Data from a modified autism screening tool revealed that XGS shares significant overlap with autism spectrum disorders. These details of the phenotypic heterogeneity of XGS implicate specific genotype/phenotype correlations and suggest potential clinical management guidelines.

KEYWORDS:

AHDC1; de novo mutation; intellectual disability

PMID:
29696776
PMCID:
PMC6231716
DOI:
10.1002/ajmg.a.38699
[Indexed for MEDLINE]
Free PMC Article

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