Clinical and genetic characterization of individuals with predicted deleterious PHIP variants.
Fiche publication
Date publication
juin 2019
Journal
Cold Spring Harbor molecular case studies
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence
Tous les auteurs :
Craddock KE, Okur V, Wilson A, Gerkes EH, Ramsey K, Heeley JM, Juusola J, Vitobello A, Bonnet Dupeyron MN, Faivre L, Chung WK
Lien Pubmed
Résumé
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 (4 frameshift, 3 missense, 2 nonsense, and 1 splice site; 6 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.
Mots clés
2-3 toe cutaneous syndactyly, Abdominal obesity, Aggressive behavior, Almond-shaped palpebral fissure, Amblyopia, Anteverted nares, Attention deficit hyperactivity disorder, Autism, Blurred vision, Chronic constipation, Chronic fatigue, Clinodactyly of the 5th finger, Gastroesophageal reflux, Generalized neonatal hypotonia, High forehead, Intellectual disability, mild, Mild global developmental delay, Synophrys, Thickened helices, Thin upper lip vermilion
Référence
Cold Spring Harb Mol Case Stud. 2019 Jun 5;: