Abstract
BackgroundRNA polymerase III-related or 4H leukodystrophy (POLR3-HLD) is an autosomal recessive hypomyelinating leukodystrophy characterized by neurological dysfunction, hypodontia and hypogonadotropic hypogonadism. The disease is caused by biallelic pathogenic variants inPOLR3A,POLR3B,POLR1CorPOLR3K. Craniofacial abnormalities reminiscent of Treacher Collins syndrome have been originally described in patients with POLR3-HLD caused by biallelic pathogenic variants inPOLR1C. To date, no published studies have appraised in detail the craniofacial features of patients with POLR3-HLD. In this work, the specific craniofacial characteristics of patients with POLR3-HLD associated with biallelic pathogenic variants inPOLR3A,POLR3BandPOLR1Care described.MethodsThe craniofacial features of 31 patients with POLR3-HLD were evaluated, and potential genotype–phenotype associations were evaluated.ResultsVarious craniofacial abnormalities were recognized in this patient cohort, with each individual presenting at least one craniofacial abnormality. The most frequently identified features included a flat midface (61.3%), a smooth philtrum (58.0%) and a pointed chin (51.6%). In patients withPOLR3Bbiallelic variants, a thin upper lip was frequent. Craniofacial anomalies involving the forehead were most commonly associated with biallelic variants inPOLR3AandPOLR3Bwhile a higher proportion of patients withPOLR1Cbiallelic variants demonstrated bitemporal narrowing.ConclusionThrough this study, we demonstrated that craniofacial abnormalities are common in patients with POLR3-HLD. This report describes in detail the dysmorphic features of POLR3-HLD associated with biallelic variants inPOLR3A,POLR3BandPOLR1C.
Funder
Leuco-Action
Fondation de l'Hôpital de Montréal pour enfants
Children’s Mercy Research Institute and Genomic Answers for Kids program at Children’s Mercy Kansas City
Canadian Research Chair CRC-II on the Neurobiology of epilepsy
Fonds de Recherche du Quebec – Santé
Canadian Institutes of Health Research
CIHR
Subject
Genetics (clinical),Genetics
Cited by
1 articles.
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