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Am J Med Genet A. 2019 Mar;179(3):344-349. doi: 10.1002/ajmg.a.61024. Epub 2019 Jan 13.

Refining the Primrose syndrome phenotype: A study of five patients with ZBTB20 de novo variants and a review of the literature.

Author information

1
South West Thames Regional Genetics Service, St. George's University Hospitals NHS Foundation Trust, London, United Kingdom.
2
Peninsula Clinical Genetics Service, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom.
3
East of Scotland Regional Genetics Service, Dundee, United Kingdom.
4
Department of Clinical Genetics, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
5
West Midlands Regional Genetics Service, Birmingham, United Kingdom.
6
Oxford Centre for Genomic Medicine, Oxford, United Kingdom.
7
Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.
8
Wessex Clinical Genetics Service, Southampton, United Kingdom.
9
Department of Human Genetics and Genomic Medicine, Southampton University, Southampton, United Kingdom.
10
Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University, Cardiff, United Kingdom.
11
Clinical Genetics Service, University Hospitals Bristol, Bristol, United Kingdom.
12
Deciphering Developmental Disorders Study, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
13
Sheffield Children's NHS Foundation Trust, Sheffield Clinical Genetics Service, Sheffield, South Yorkshire, United Kingdom.
14
St. George's University of London, London, United Kingdom.

Abstract

Primrose syndrome is a rare autosomal dominant condition caused by heterozygous missense variants within ZBTB20. Through an exome sequencing approach (as part of the Deciphering Developmental Disorders [DDD] study) we have identified five unrelated individuals with previously unreported, de novo ZBTB20 pathogenic missense variants. All five missense variants targeted the C2H2 zinc finger domains. This genotype-up approach has allowed further refinement of the Primrose syndrome phenotype. Major characteristics (>90% individuals) include an intellectual disability (most frequently in the moderate range), a recognizable facial appearance and brain MRI abnormalities, particularly abnormalities of the corpus callosum. Other frequent clinical associations (in 50-90% individuals) include sensorineural hearing loss (83%), hypotonia (78%), cryptorchidism in males (75%), macrocephaly (72%), behavioral issues (56%), and dysplastic/hypoplastic nails (57%). Based upon these clinical data we discuss our current management of patients with Primrose syndrome.

KEYWORDS:

DDD study; Primrose syndrome; ZBTB20; exome sequencing; intellectual disability

PMID:
30637921
DOI:
10.1002/ajmg.a.61024

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