Broadening the PHIP -Associated Neurodevelopmental Phenotype.

Background: Monoallelic damaging variants in PHIP (MIM*612870), encoding the Pleckstrin Homology Domain Interacting Protein, have been associated with a novel neurodevelopmental disorder, also termed Chung–Jansen syndrome (CHUJANS, MIM#617991). Most of the described individuals show developmental de...

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Publicado en:Children Vol. 11; no. 11; pp. 1395 - 1404
Autores principales: Pascolini, Giulia, Scaglione, Giovanni Luca, Chandramouli, Balasubramanian, Castiglia, Daniele, Di Zenzo, Giovanni, Didona, Biagio
Formato: case study pictorial tables/charts Journal Article
Publicado: MDPI Nov2024
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Nov2024
      vid: 11
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      pub: MDPI
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        10.3390/children11111395
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        atl: Broadening the PHIP -Associated Neurodevelopmental Phenotype.
      aug:
        au:
          Pascolini, Giulia
          Scaglione, Giovanni Luca
          Chandramouli, Balasubramanian
          Castiglia, Daniele
          Di Zenzo, Giovanni
          Didona, Biagio
        affil: Genetic Counselling Unit, Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy
      sug:
        subj:
          Chromosome Disorders
          Developmental Disabilities
          Intellectual Disability
          Abnormalities, Multiple Diagnosis
          Male
          Child
          Obesity
          Genome
          Sequence Analysis
          Genetic Techniques
          Proteins Metabolism
          Bioinformatics
          Child: 6-12 years
          Male
      ab: Background: Monoallelic damaging variants in PHIP (MIM*612870), encoding the Pleckstrin Homology Domain Interacting Protein, have been associated with a novel neurodevelopmental disorder, also termed Chung–Jansen syndrome (CHUJANS, MIM#617991). Most of the described individuals show developmental delay (DD)/intellectual disability (ID), obesity/overweight, and variable congenital anomalies, so the condition can be considered as an ID–overweight syndrome. Case Description: We evaluated a child presenting with DD/ID and a craniofacial phenotype reminiscent of a Pitt–Hopkins syndrome (PTHS)-like condition. We performed a clinical exome analysis on his biological sample, as well as an in silico prediction of the obtained data. At the same time, we interrogated the DeepGestalt technology powered by Face2Gene (F2G), using a frontal image of the proband, and clinically reviewed the earlier CHUJANS patients. In this child, we found a novel PHIP pathogenetic variant, which we corroborated through a protein modeling approach. The F2G platform supported the initial clinical hypothesis of a PTHS-like condition, while the clinical review highlighted the lack of the main frequent CHUJANS clinical features in this child. Conclusions: The unusual clinical presentation of this novel patient resembles a PTHS-like condition. However, a novel variant in PHIP has been unexpectedly detected, expanding the phenotypic spectrum of CHUJANS. Notably, PTHS (MIM#610954), which is a different ID syndrome caused by heterozygous variants in TCF4 (MIM*610954), is not classically considered in the differential diagnosis of CHUJANS nor has been cited in the previous studies. This could support other complex diagnoses and invite further patients' descriptions.
      pubtype: Academic Journal
      doctype:
        case study
        pictorial
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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