Genotypes and phenotypes of capillary malformation-arteriovenous malformation: characterization and correlation analysis.
capillary malformation‐arteriovenous malformation
gene frequency
genetic association studies
genetics
humans
mutation
phenotype
trigeminal nerve
Journal
International journal of dermatology
ISSN: 1365-4632
Titre abrégé: Int J Dermatol
Pays: England
ID NLM: 0243704
Informations de publication
Date de publication:
04 Oct 2024
04 Oct 2024
Historique:
revised:
08
09
2024
received:
31
05
2024
accepted:
14
09
2024
medline:
5
10
2024
pubmed:
5
10
2024
entrez:
5
10
2024
Statut:
aheadofprint
Résumé
Capillary malformation-arteriovenous malformation (CM-AVM) is a rare genetic disorder characterized by multiple small capillary malformations (CMs) and arteriovenous malformations (AVMs), which has been linked with pathogenic variants in RASA1 and EPHB4. However, more data are needed to explore the phenotypic characteristics and the association between genotypes and clinical phenotypes. Our aim was to investigate the phenotypic and genetic characteristics of CM-AVM in East Asians, identify potential unique phenotypes, and conduct genotype-phenotype association analyses. This is a single-center study prospectively collecting CM-AVM patients' clinical data, with genetic data from blood or tissue samples. A total of 59 patients were enrolled. Thirty-two individuals had a leading CM greater than Schobinger stage II. The trigeminal nerve branches and greater auricular, transverse cervical, and lesser occipital nerves' somatosensory innervation zones divided head and neck CMs into six zones: V1, V2, V3, GA, TC, and LO zones. GA, TC, and LO zones had a positive correlation with one another but a negative correlation with V2 zone involvement. The RASA1 and EPHB4 pathogenic variants were detected in 41 out of 59, which showed two types of variant allele frequency (VAF) distributions. VAF above 30% made RASA1 pathogenic variants more susceptible to multifocal CMs than those below 30%. Leading CMs in the head and neck exhibit two segmentation patterns, anterior and lateral, which may differ in ear involvement and progression. Germline RASA1 pathogenic variants increased multifocal CM risk more than the somatic variants.
Sections du résumé
BACKGROUND
BACKGROUND
Capillary malformation-arteriovenous malformation (CM-AVM) is a rare genetic disorder characterized by multiple small capillary malformations (CMs) and arteriovenous malformations (AVMs), which has been linked with pathogenic variants in RASA1 and EPHB4. However, more data are needed to explore the phenotypic characteristics and the association between genotypes and clinical phenotypes.
OBJECTIVES
OBJECTIVE
Our aim was to investigate the phenotypic and genetic characteristics of CM-AVM in East Asians, identify potential unique phenotypes, and conduct genotype-phenotype association analyses.
METHODS
METHODS
This is a single-center study prospectively collecting CM-AVM patients' clinical data, with genetic data from blood or tissue samples.
RESULTS
RESULTS
A total of 59 patients were enrolled. Thirty-two individuals had a leading CM greater than Schobinger stage II. The trigeminal nerve branches and greater auricular, transverse cervical, and lesser occipital nerves' somatosensory innervation zones divided head and neck CMs into six zones: V1, V2, V3, GA, TC, and LO zones. GA, TC, and LO zones had a positive correlation with one another but a negative correlation with V2 zone involvement. The RASA1 and EPHB4 pathogenic variants were detected in 41 out of 59, which showed two types of variant allele frequency (VAF) distributions. VAF above 30% made RASA1 pathogenic variants more susceptible to multifocal CMs than those below 30%.
CONCLUSIONS
CONCLUSIONS
Leading CMs in the head and neck exhibit two segmentation patterns, anterior and lateral, which may differ in ear involvement and progression. Germline RASA1 pathogenic variants increased multifocal CM risk more than the somatic variants.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Top Priority Research Center of Shanghai - Plastic Surgery Research Center, Shanghai
ID : 2023ZZ02023
Organisme : Fundamental Research Funds for the Central Universities
ID : YG2023ZD13
Organisme : Commercial Research Funds of Shanghai Ninth People's Hospital
ID : JYHX2022015
Organisme : Major and Key Cultivation Projects of Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine
ID : JYZP005
Organisme : Rare Disease Registration Platform of Shanghai Ninth People's Hospital
ID : JYHJB02
Informations de copyright
© 2024 the International Society of Dermatology.
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