Genetic characterization of Schuurs-Hoeijmakers syndrome in a moroccan individual with heterozygote PACS1 mutation.
Exome sequencing
Genetic mutation
Intellectual disability
PACS1
Schuurs-Hoeijmakers
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
21
07
2023
accepted:
06
09
2023
medline:
10
11
2023
pubmed:
25
9
2023
entrez:
25
9
2023
Statut:
ppublish
Résumé
Schuurs-Hoeijmakers syndrome, an autosomal dominant neurodevelopmental genetic disorder, is a rare cause of intellectual disability (ID) affecting approximately 1 to 3% of all over the world. Only 87 cases have been recorded to date, and oddly enough, the majority of them share the same mutation (c.607 C > T; p.R203W). This study presents the first reported case in Morocco of a 12-year-old female patient with PACS1 syndrome, identified during a cohort study of 24 patients with intellectual disability. The syndrome is caused by a de novo mutation of the PACS1 gene, located on chromosome 11, resulting in a single amino acid modification on the PACS1 protein. The abnormal protein disrupts cellular transport processes, leading to intellectual developmental delay, facial dysmorphia, and congenital anomalies. Exome sequencing was employed to identify the genetic mutation, and Sanger sequencing validated the presence of the recurrent mutation c.607 C > T (p.Arg203Trp) in the PACS1 gene. The mutation was found to be heterozygous and de novo, suggesting that it was not inherited from the patient's parents. Classification based on the American College of Medical Genetics and Genomics (ACMG) criteria confirmed its pathogenicity, with supporting evidence from bioinformatics analysis. The rarity of this variant in population databases further supports its pathogenic nature. This study expands our understanding of Schuurs-Hoeijmakers syndrome, a disorder with limited reported cases globally. The genetic heterogeneity of the disorder is highlighted, with the recurrent mutation being the most common pathogenic variant. Functional studies indicate the crucial role of PACS1 in craniofacial development and neurodevelopmental processes, with potential implications for autism spectrum disorders (ASD). Comprehensive genetic analyses are essential for accurate diagnosis and understanding the underlying causes of intellectual disabilities. Further research is warranted to unravel the mechanisms and potential therapeutic targets associated with PACS1-related neurodevelopmental disorders.
Sections du résumé
BACKGROUND
BACKGROUND
Schuurs-Hoeijmakers syndrome, an autosomal dominant neurodevelopmental genetic disorder, is a rare cause of intellectual disability (ID) affecting approximately 1 to 3% of all over the world. Only 87 cases have been recorded to date, and oddly enough, the majority of them share the same mutation (c.607 C > T; p.R203W).
CASE PRESENTATION
METHODS
This study presents the first reported case in Morocco of a 12-year-old female patient with PACS1 syndrome, identified during a cohort study of 24 patients with intellectual disability. The syndrome is caused by a de novo mutation of the PACS1 gene, located on chromosome 11, resulting in a single amino acid modification on the PACS1 protein. The abnormal protein disrupts cellular transport processes, leading to intellectual developmental delay, facial dysmorphia, and congenital anomalies.
METHODS AND RESULTS
RESULTS
Exome sequencing was employed to identify the genetic mutation, and Sanger sequencing validated the presence of the recurrent mutation c.607 C > T (p.Arg203Trp) in the PACS1 gene. The mutation was found to be heterozygous and de novo, suggesting that it was not inherited from the patient's parents. Classification based on the American College of Medical Genetics and Genomics (ACMG) criteria confirmed its pathogenicity, with supporting evidence from bioinformatics analysis. The rarity of this variant in population databases further supports its pathogenic nature.
CONCLUSION
CONCLUSIONS
This study expands our understanding of Schuurs-Hoeijmakers syndrome, a disorder with limited reported cases globally. The genetic heterogeneity of the disorder is highlighted, with the recurrent mutation being the most common pathogenic variant. Functional studies indicate the crucial role of PACS1 in craniofacial development and neurodevelopmental processes, with potential implications for autism spectrum disorders (ASD). Comprehensive genetic analyses are essential for accurate diagnosis and understanding the underlying causes of intellectual disabilities. Further research is warranted to unravel the mechanisms and potential therapeutic targets associated with PACS1-related neurodevelopmental disorders.
Identifiants
pubmed: 37747683
doi: 10.1007/s11033-023-08803-9
pii: 10.1007/s11033-023-08803-9
doi:
Substances chimiques
PACS1 protein, human
0
Vesicular Transport Proteins
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9121-9128Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
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