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

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

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.

DDD study, exome sequencing, intellectual disability, Primrose syndrome, ZBTB20
1552-4825
344-349
Cleaver, Ruth
59105614-b9da-4a64-b436-6203ca096b6a
Berg, Jonathan
b05b030d-b9e1-4c89-b3da-57c6c67c772f
Craft, Emily
c9bf4074-32cd-4301-8d3b-3bad8c00b606
Foster, Alison
b4c17aed-1b91-4d83-84b7-612248476158
Gibbons, Richard J.
a6222c72-0f75-43af-bb65-c383bdb85277
Hobson, Emma
871d8e83-04a0-45f8-af70-73e4a2fd3a22
Lachlan, Katherine
175ce889-ede8-477e-93eb-afefc1af5dda
Naik, Swati
263c3c6d-0ab0-4c20-8d0b-705790fa2ce4
Sampson, Julian R.
3c5832fb-abbb-4781-b931-5b5acd579466
Sharif, Saba
9e976d1f-c6b2-4278-a2ea-40cc813269ad
Smithson, Sarah
06d43b21-3efb-413b-b593-2b8f7804d3ef
Parker, Michael J.
9a223cab-0ee5-417e-93e4-199f139f3ffc
Tatton-Brown, Katrina
dbad5eb1-70eb-4fde-8f67-a37ff32ef9c6
Deciphering Developmental Disorders Study
Cleaver, Ruth
59105614-b9da-4a64-b436-6203ca096b6a
Berg, Jonathan
b05b030d-b9e1-4c89-b3da-57c6c67c772f
Craft, Emily
c9bf4074-32cd-4301-8d3b-3bad8c00b606
Foster, Alison
b4c17aed-1b91-4d83-84b7-612248476158
Gibbons, Richard J.
a6222c72-0f75-43af-bb65-c383bdb85277
Hobson, Emma
871d8e83-04a0-45f8-af70-73e4a2fd3a22
Lachlan, Katherine
175ce889-ede8-477e-93eb-afefc1af5dda
Naik, Swati
263c3c6d-0ab0-4c20-8d0b-705790fa2ce4
Sampson, Julian R.
3c5832fb-abbb-4781-b931-5b5acd579466
Sharif, Saba
9e976d1f-c6b2-4278-a2ea-40cc813269ad
Smithson, Sarah
06d43b21-3efb-413b-b593-2b8f7804d3ef
Parker, Michael J.
9a223cab-0ee5-417e-93e4-199f139f3ffc
Tatton-Brown, Katrina
dbad5eb1-70eb-4fde-8f67-a37ff32ef9c6

Cleaver, Ruth, Berg, Jonathan, Craft, Emily, Foster, Alison, Gibbons, Richard J., Hobson, Emma, Lachlan, Katherine, Naik, Swati, Sampson, Julian R., Sharif, Saba, Smithson, Sarah, Parker, Michael J. and Tatton-Brown, Katrina , Deciphering Developmental Disorders Study (2019) Refining the Primrose syndrome phenotype: A study of five patients with ZBTB20 de novo variants and a review of the literature. American Journal of Medical Genetics: Part A, 179 (3), 344-349. (doi:10.1002/ajmg.a.61024).

Record type: Article

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.

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More information

Accepted/In Press date: 29 November 2018
e-pub ahead of print date: 13 January 2019
Published date: March 2019
Keywords: DDD study, exome sequencing, intellectual disability, Primrose syndrome, ZBTB20

Identifiers

Local EPrints ID: 430145
URI: https://eprints.soton.ac.uk/id/eprint/430145
ISSN: 1552-4825
PURE UUID: a0899798-876c-48fc-941a-e68cdf693d42

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Date deposited: 12 Apr 2019 16:30
Last modified: 12 Apr 2019 16:30

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Contributors

Author: Ruth Cleaver
Author: Jonathan Berg
Author: Emily Craft
Author: Alison Foster
Author: Richard J. Gibbons
Author: Emma Hobson
Author: Katherine Lachlan
Author: Swati Naik
Author: Julian R. Sampson
Author: Saba Sharif
Author: Sarah Smithson
Author: Michael J. Parker
Author: Katrina Tatton-Brown

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