Syndromic intellectual disability and developmental delay caused by novel de novo truncating variant in AHDC1 gene

Introduction: Xia-Gibbs syndrome is a rare genetic disorder with autosomal dominant inheritance caused by heterozygous mutations in AHDC1 gene. This condition is characterized by neurological manifestations that include psychomotor delayed, intellectual disability and corpus callosum hypoplasia with distinct facial features. Case report: We present a 13 years-old female from Colombia, born to non-consanguineous parents. She was diagnosed at age of 2 years for psychomotor and language delay, facial dysmorphic features and sleep apnea with plagiocephaly. She has associated behavioral disorders that include self-harm, poor social interaction with isolation. Results: Chromosome analysis was normal (Kariotyping and CGH-array). WES (Whole Exome Sequencing) was performed at 12 years and revealed a novel heterozygous de novo frameshift variant c.1529delG (p.Gly510Alafs*12) in AHDC1 gene (NM_001029882.3), variant functional prediction software tools Mutation tester, Polyphen-2, and SIFT classified it as a deleterious variant. Discussion: The mutation reported here introduces a stop codon at the amino acid 522 of AHDC1 protein (1603 amino acids). This leads to the loss of one DNA-binding motif and PDZ carboxyl-terminal domain, which could truncate its interaction with other proteins and can be related to the neurobehavioural manifestations in our patient.

• Autores: Diaz Ordoñez, L.; Ramirez Montaño, D.; Cruz, S.; Pachajoa, H.
• Tipo de recurso: Article of journal
• Fecha de publicación: 2019
• Institución: Universidad El Bosque
• Repositorio: Repositorio U. El Bosque
• Idioma: eng
• OAI Identifier: oai:repositorio.unbosque.edu.co:20.500.12495/7383
• Acceso en línea: http://hdl.handle.net/20.500.12495/7383
• Palabra clave: Síndrome de Xia-Gibbs; Trastornos genéticos; Gen AHDC1; Estudio de caso; Análisis cromosómico; Xia–Gibbs syndrome; Genetic disorders; AHDC1 gene; Case study
• Rights: openAccess
• License: Atribución-NoComercial-CompartirIgual 4.0 Internacional