Phenotypic variability in Joubert syndrome is partially explained by ciliary pathophysiology.
Ann Hum Genet
; 88(1): 86-100, 2024 01.
Article
en En
| MEDLINE
| ID: mdl-37921557
ABSTRACT
INTRODUCTION:
Joubert syndrome (JS) arises from defects of primary cilia resulting in potential malformations of the brain, kidneys, eyes, liver, and limbs. Several of the 35+ genes associated with JS have recognized genotype/phenotype correlations, but most genes have not had enough reported individuals to draw meaningful conclusions.METHODS:
A PubMed literature review identified 688 individuals with JS across 32 genes and 112 publications to bolster known genotype/phenotype relationships and identify new correlations. All included patients had the "molar tooth sign" and a confirmed genetic diagnosis. Individuals were categorized by age, ethnicity, sex and the presence of developmental disability/intellectual disability, hypotonia, abnormal eye movements, ataxia, visual impairment, renal impairment, polydactyly, and liver abnormalities.RESULTS:
Most genes demonstrated unique phenotypic profiles. Grouping proteins based on physiologic interactions established stronger phenotypic relationships that reflect known ciliary pathophysiology. Age-stratified data demonstrated that end-organ disease is progressive in JS. Most genes demonstrated a significant skew towards having variants with either residual protein function or no residual protein function.CONCLUSION:
This cohort demonstrates that clinically meaningful genotype/phenotype relationships exist within most JS-related genes and can be referenced to allow for more personalized clinical care.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Anomalías Múltiples
/
Anomalías del Ojo
/
Enfermedades Renales Quísticas
Límite:
Humans
Idioma:
En
Revista:
Ann Hum Genet
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos