Evidence that homozygous PTPRD gene microdeletion causes trigonocephaly, hearing loss, and intellectual disability
| Autor: | Ali Fawaz, Pierre Cacciagli, Laurent Villard, Cécile Mignon-Ravix, André Mégarbané, Nancy Choucair, Joelle Abou Ghoch, Eliane Chouery |
|---|---|
| Přispěvatelé: | Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de génétique médicale, Université Saint-Joseph de Beyrouth (USJ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropediatrics Department, Lebanese International University (LIU), Institut Jérôme Lejeune, HAL AMU, Administrateur |
| Jazyk: | angličtina |
| Předmět: |
Monosomy 9p
SYMPTOMS [SDV]Life Sciences [q-bio] Intellectual disability Case Report [SDV.GEN] Life Sciences [q-bio]/Genetics Bioinformatics Biochemistry 0302 clinical medicine Trigonocephaly Genetics(clinical) Hypertelorism 10. No inequality Genetics (clinical) Genetics 0303 health sciences [SDV] Life Sciences [q-bio] CELL-ADHESION MOLECULE CRITICAL REGION Molecular Medicine medicine.symptom SIGMA 9P SYNDROME Hearing loss [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics PATIENT Craniosynostosis 03 medical and health sciences medicine Metopic synostosis Molecular Biology 030304 developmental biology Biochemistry medical [SDV.GEN]Life Sciences [q-bio]/Genetics DELTA business.industry DELETION Biochemistry (medical) medicine.disease Protein tyrosine phosphatase receptor delta PTPRD Gene PROTEIN-TYROSINE PHOSPHATASES LAR [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics business 030217 neurology & neurosurgery |
| Zdroj: | Molecular Cytogenetics Molecular Cytogenetics, 2015, ⟨10.1186/s13039-015-0149-0⟩ Molecular Cytogenetics, BioMed Central, 2015, ⟨10.1186/s13039-015-0149-0⟩ |
| ISSN: | 1755-8166 |
| DOI: | 10.1186/s13039-015-0149-0 |
| Popis: | International audience; Background: The premature fusion of metopic sutures results in the clinical phenotype of trigonocephaly. An association of this characteristic with the monosomy 9p syndrome is well established and the receptor-type protein tyrosine phosphatase gene (PTPRD), located in the 9p24.1p23 region and encoding a major component of the excitatory and inhibitory synaptic organization, is considered as a good candidate to be responsible for this form of craniosynostosis. Moreover PTPRD is known to recruit multiple postsynaptic partners such as IL1RAPL1 which gene alterations lead to non syndromic intellectual disability (ID). Results: We describe a 30 month old boy with severe intellectual disability, trigonocephaly and dysmorphic facial features such as a midface hypoplasia, a flat nose, a depressed nasal bridge, hypertelorism, a long philtrum and a drooping mouth. Microarray chromosomal analysis revealed the presence of a homozygous deletion involving the PTPRD gene, located on chromosome 9p22.3. Reverse Transcription PCR (RT- PCR) amplifications all along the gene failed to amplify the patient's cDNA in fibroblasts, indicating the presence of two null PTPRD alleles. Synaptic PTPRD interacts with IL1RAPL1 which defects have been associated with intellectual disability (ID) and autism spectrum disorder. The absence of the PTPRD transcript leads to a decrease in the expression of IL1RAPL1. These results suggest the direct involvement of PTPRD in ID, which is consistent with the PTPRD -/- mice phenotype. Deletions of PTPRD have been previously suggested as a cause of trigonocephaly in patients with monosomy 9p and genome-wide association study suggested variations in PTPRD are associated with hearing loss. Conclusions: The deletion identified in the reported patient supports previous hypotheses on its function in ID and hearing loss. However, its involvement in the occurrence of metopic synostosis is still to be discussed as more investigation of patients with the 9p monosomy syndrome is required. |
| Databáze: | OpenAIRE |
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