Aggrecan-related bone disorders; a novel heterozygous ACAN variant associated with spondyloepimetaphyseal dysplasia expanding the phenotypic spectrum and review of literature.
ACAN
Heterozygous
Skeletal dysplasias
Journal
Journal, genetic engineering & biotechnology
ISSN: 2090-5920
Titre abrégé: J Genet Eng Biotechnol
Pays: Netherlands
ID NLM: 101317150
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
medline:
18
3
2024
pubmed:
18
3
2024
entrez:
17
3
2024
Statut:
ppublish
Résumé
Spondyloepimetaphyseal dysplasias (SEMD) are a large group of skeletal disorders represented by abnormalities of vertebrae in addition to epiphyseal and metaphyseal areas of bones. Several genes have been identified underlying different forms. ACAN gene mutations were found to cause Aggrecan-related bone disorders (spondyloepimetaphyseal dysplasias,spondyloepiphyseal dysplasias, familial osteochondritis dissecans and short stature syndromes). This study aims to find the disease causing variant in Egyptian patient with SEMD using whole exome sequencing. Whole-exome sequencing was performed for an Egyptian male patient who presented with short stature, clinical and radiological features suggestive of unclassified SEMD. The study identified a novel de novo heterozygous ACAN gene variant (c.7378G>A; p.Gly2460Arg) in G3 domain. Mutations in ACAN gene have been more commonly associated with short stature than SEMD. The phenotype of our patient was intermediate in severity between spondyloepiphyseal dysplasia presentation; Kimberley type(SEDK) and Spondyloepimetaphyseal dysplasias Aggrecan (SEMDAG) CONCLUSIONS: Whole exome sequencing revealed a novel de novo ACAN gene variant in patient with SEDK. The clinical and skeletal phenotype of our patient was much severe than those reported originally and showed more metaphyseal involvement. To the best of our knowledge, two previous studies reported a heterozygous variant in ACAN with spondyloepiphyseal dysplasia presentation; Kimberley type.
Sections du résumé
BACKGROUND
BACKGROUND
Spondyloepimetaphyseal dysplasias (SEMD) are a large group of skeletal disorders represented by abnormalities of vertebrae in addition to epiphyseal and metaphyseal areas of bones. Several genes have been identified underlying different forms. ACAN gene mutations were found to cause Aggrecan-related bone disorders (spondyloepimetaphyseal dysplasias,spondyloepiphyseal dysplasias, familial osteochondritis dissecans and short stature syndromes). This study aims to find the disease causing variant in Egyptian patient with SEMD using whole exome sequencing.
METHODS
METHODS
Whole-exome sequencing was performed for an Egyptian male patient who presented with short stature, clinical and radiological features suggestive of unclassified SEMD.
RESULTS
RESULTS
The study identified a novel de novo heterozygous ACAN gene variant (c.7378G>A; p.Gly2460Arg) in G3 domain. Mutations in ACAN gene have been more commonly associated with short stature than SEMD. The phenotype of our patient was intermediate in severity between spondyloepiphyseal dysplasia presentation; Kimberley type(SEDK) and Spondyloepimetaphyseal dysplasias Aggrecan (SEMDAG) CONCLUSIONS: Whole exome sequencing revealed a novel de novo ACAN gene variant in patient with SEDK. The clinical and skeletal phenotype of our patient was much severe than those reported originally and showed more metaphyseal involvement. To the best of our knowledge, two previous studies reported a heterozygous variant in ACAN with spondyloepiphyseal dysplasia presentation; Kimberley type.
Identifiants
pubmed: 38494255
pii: S1687-157X(23)01512-3
doi: 10.1016/j.jgeb.2023.100341
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100341Informations de copyright
Copyright © 2024 Academy of Scientific Research and Technology. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.