Clinical and genetic characterization of individuals with predicted deleterious PHIP variants.

Autor:	Craddock KE; Vagelos College of Physicians and Surgeons, New York, New York 10032, USA., Okur V; Department of Pediatrics, Columbia University, New York, New York 10032, USA., Wilson A; Department of Pediatrics, Columbia University, New York, New York 10032, USA., Gerkes EH; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, 9713 D2, Netherlands., Ramsey K; Center for Rare Childhood Disorders, Translational Genomics Research Institute, Phoenix, Arizona 85012, USA., Heeley JM; Mercy Clinic-Kids Genetics, Mercy Children's Hospital, St. Louis, Missouri 63141, USA., Juusola J; GeneDx, Gaithersburg, Maryland, 20877, USA., Vitobello A; Centre de Reference Anomalies of the Developpement et Syndromes Malformatifs, Dijon University Hospital, Dijon, 21079, France., Dupeyron MB; Hospital of Valence, Genetic Consultations, Valence, 26000, France., Faivre L; Centre de Reference Anomalies of the Developpement et Syndromes Malformatifs, Dijon University Hospital, Dijon, 21079, France., Chung WK; Department of Pediatrics, Columbia University, New York, New York 10032, USA.; Department of Medicine, Columbia University, New York, New York 10032, USA.
Jazyk:	angličtina
Zdroj:	Cold Spring Harbor molecular case studies [Cold Spring Harb Mol Case Stud] 2019 Aug 01; Vol. 5 (4). Date of Electronic Publication: 2019 Aug 01 (Print Publication: 2019).
DOI:	10.1101/mcs.a004200
Abstrakt:	Heterozygous deleterious variants in PHIP have been associated with behavioral problems, intellectual disability/developmental delay, obesity/overweight, and dysmorphic features (BIDOD syndrome). We report an additional 10 individuals with pleckstrin homology domain-interacting protein ( PHIP )-predicted deleterious variants (four frameshift, three missense, two nonsense, and one splice site; six of which are confirmed de novo). The mutation spectrum is diverse, and there is no clustering of mutations across the protein. The clinical phenotype of these individuals is consistent with previous reports and includes behavioral problems, intellectual disability, developmental delay, hypotonia, and dysmorphic features. The additional individuals we report have a lower frequency of obesity than previous reports and a higher frequency of gastrointestinal problems, social deficits, and behavioral challenges. Characterizing additional individuals with diverse mutations longitudinally will provide better natural history data to assist with medical management and educational and behavioral support. (© 2019 Craddock et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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