Please use this identifier to cite or link to this item:
Title: The diverse pleiotropic effects of spliceosomal protein PUF60: A case series of Verheij syndrome.
Austin Authors: Fennell, Andrew Paul;Baxter, Anne Elizabeth;Berkovic, Samuel Frank;Ellaway, Carolyn Jane;Forwood, Caitlin;Hildebrand, Michael S ;Kumble, Smitha;McKeown, Colina;Mowat, David;Poke, Gemma;Rajagopalan, Sulekha;Regan, Brigid M;Scheffer, Ingrid E ;Stark, Zornitza;Stutterd, Chloe Alice;Tan, Tiong Yang;Wilkins, Ella Jane;Yeung, Alison;Hunter, Matthew Frank
Affiliation: Monash Genetics, Monash Health, Melbourne, Australia.
Hunter Genetics, Hunter New England Health Service, Newcastle, Australia.
Epilepsy Research Centre
Paediatrics North, Sydney, Australia.
Centre for Clinical Genetics, Sydney Children's Hospital Randwick, Sydney, Australia.
Clinical Genetics
Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia.
Genetic Health Service New Zealand, Wellington Hospital, Wellington, New Zealand.
Centre for Clinical Genetics, Sydney Children's Hospital Randwick, Sydney, Australia.
The Florey Institute of Neuroscience and Mental Health
Department of Clinical Genetics, Liverpool Hospital, Sydney, Australia.
Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia.
Monash Genetics, Monash Health, Melbourne, Australia.
Issue Date: Dec-2022 2022
Publication information: American Journal of Medical Genetics. Part A 2022; 188(12)
Abstract: 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.
DOI: 10.1002/ajmg.a.62950
ORCID: 0000-0001-6744-1810
Journal: American Journal of Medical Genetics. Part A
Start page: 3432
End page: 3447
PubMed URL: 36367278
ISSN: 1552-4833
Type: Journal Article
Subjects: 8q24.3
Verheij syndrome
craniofacial spliceosomopathy
spliceosomal disorder
Abnormalities, Multiple/diagnosis
Abnormalities, Multiple/genetics
Intellectual Disability/diagnosis
Intellectual Disability/genetics
Repressor Proteins/genetics
RNA Splicing Factors/genetics
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Jun 6, 2023

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.