A pathogenic variant in the SETBP1 hotspot results in a forme-fruste Schinzel-Giedion syndrome.


Journal

American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741

Informations de publication

Date de publication:
08 2020
Historique:
received: 05 03 2020
revised: 25 04 2020
accepted: 28 04 2020
pubmed: 24 5 2020
medline: 4 6 2021
entrez: 24 5 2020
Statut: ppublish

Résumé

Schinzel-Giedion syndrome (SGS; OMIM 269150) is an ultra-rare genetic disorder associated with a distinctive facial gestalt, congenital malformations, severe intellectual disability, and a progressive neurological course. The prognosis for SGS is poor, with survival beyond the first decade rare. Germline, de novo heterozygous variants in the SETBP1 gene cause SGS with the pathogenic variants associated with the SGS phenotype missense and confined to exon 4 of the gene, clustered in a four amino acid (12 bp) hotspot in the SKI homologous region of the SETBP1 protein. We report a patient with a de novo I871S variant within the SKI homologous region, which has been associated with the severe phenotype previously; but our patient has fewer features of SGS and a milder course. This is the first report of a forme-fruste phenotype in a patient with a pathogenic variant within the SGS hotspot on the SETBP1 gene and it highlights the importance of considering atypical clinical presentations in the context of severe ultra-rare genetic disorders.

Identifiants

pubmed: 32445275
doi: 10.1002/ajmg.a.61630
doi:

Substances chimiques

Carrier Proteins 0
Nuclear Proteins 0
SETBP1 protein, human 0

Types de publication

Case Reports

Langues

eng

Sous-ensembles de citation

IM

Pagination

1947-1951

Informations de copyright

© 2020 Wiley Periodicals, Inc.

Références

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Auteurs

Jennifer A Sullivan (JA)

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.

Nicholas Stong (N)

Institute for Genomic Medicine, Columbia University, New York, New York, USA.

Evan H Baugh (EH)

Institute for Genomic Medicine, Columbia University, New York, New York, USA.

Marie T McDonald (MT)

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.

Akihito Takeuchi (A)

Department of Neonatology, Okayama Medical Center, National Hospital Organization, Okayama, Japan.

Vandana Shashi (V)

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.

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