The diverse pleiotropic effects of spliceosomal protein PUF60: A case series of Verheij syndrome.
8q24.3
PUF60
Verheij syndrome
craniofacial spliceosomopathy
spliceosomal disorder
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
17
05
2022
received:
20
02
2022
accepted:
11
06
2022
entrez:
11
11
2022
pubmed:
12
11
2022
medline:
15
11
2022
Statut:
ppublish
Résumé
Verheij syndrome (VRJS) is a rare craniofacial spliceosomopathy presenting with craniofacial dysmorphism, multiple congenital anomalies and variable neurodevelopmental delay. It is caused by single nucleotide variants (SNVs) in PUF60 or interstitial deletions of the 8q24.3 region. PUF60 encodes a splicing factor which forms part of the spliceosome. To date, 36 patients with a sole diagnosis of VRJS due to disease-causing PUF60 SNVs have been reported in peer-reviewed publications. Although the depth of their phenotyping has varied greatly, they exhibit marked phenotypic heterogeneity. We report 10 additional unrelated patients, including the first described patients of Khmer, Indian, and Vietnamese ethnicities, and the eldest patient to date, with 10 heterozygous PUF60 variants identified through exome sequencing, 8 previously unreported. All patients underwent deep phenotyping identifying variable dysmorphism, growth delay, neurodevelopmental delay, and multiple congenital anomalies, including several unique features. The eldest patient is the only reported individual with a germline variant and neither neurodevelopmental delay nor intellectual disability. In combining these detailed phenotypic data with that of previously reported patients (n = 46), we further refine the known frequencies of features associated with VRJS. These include neurodevelopmental delay/intellectual disability (98%), axial skeletal anomalies (74%), appendicular skeletal anomalies (73%), oral anomalies (68%), short stature (66%), cardiac anomalies (63%), brain malformations (48%), hearing loss (46%), microcephaly (41%), colobomata (38%), and other ocular anomalies (65%). This case series, incorporating three patients from previously unreported ethnic backgrounds, further delineates the broad pleiotropy and mutational spectrum of PUF60 pathogenic variants.
Identifiants
pubmed: 36367278
doi: 10.1002/ajmg.a.62950
doi:
Substances chimiques
Repressor Proteins
0
RNA Splicing Factors
0
poly-U binding splicing factor 60KDa
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3432-3447Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
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