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Successful pregnancies in an adult with Meier-Gorlin syndrome harbouring biallelic CDT1 variants

Successful pregnancies in an adult with Meier-Gorlin syndrome harbouring biallelic CDT1 variants
Successful pregnancies in an adult with Meier-Gorlin syndrome harbouring biallelic CDT1 variants
Meier-Gorlin syndrome is an autosomal recessively inherited disorder of growth retardation, accompanied by microtia and patellae a/hypoplasia and characteristic facies. Pathogenic variants in genes associated with the initiation of DNA replication underlie the condition, with biallelic variants in CDT1 the most common cause. Using 10X Chromium genome sequencing, we report CDT1 variants in an adult female, with an inframe amino acid deletion inherited in trans with a deep intronic variant which likely serves as the branchpoint site in intron 8. Splicing defects arising from this variant were confirmed through in vitro analysis. At 49 years, she represents the oldest patient with a molecular diagnosis described in the literature and is the first reported patient with Meier-Gorlin syndrome to have carried a successful pregnancy to term. Both of her pregnancies were complicated by postpartum haemorrhage and upon subsequent necessary hysterectomy, revealed uterine abnormalities. There is scant knowledge on reproductive ability and success in patients with Meier-Gorlin syndrome. Successful pregnancies amongst other clinically recognisable forms of primordial dwarfism have also not been described previously. This case is therefore of clinical interest for many forms of inherited growth retardation, and will assist in providing more information and clinical guidance for females of reproductive age
1552-4825
Knapp, Karen M
871bf3cb-85d2-4a7f-929f-7b2c3033cd2e
Murray, Jennie E.
b5971302-dc74-41b4-90eb-001743066be7
Temple, Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Bicknell, Louise S.
9c95ab98-830f-44a8-b2fb-ac3df8bceec8
Knapp, Karen M
871bf3cb-85d2-4a7f-929f-7b2c3033cd2e
Murray, Jennie E.
b5971302-dc74-41b4-90eb-001743066be7
Temple, Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Bicknell, Louise S.
9c95ab98-830f-44a8-b2fb-ac3df8bceec8

Knapp, Karen M, Murray, Jennie E., Temple, Karen and Bicknell, Louise S. (2020) Successful pregnancies in an adult with Meier-Gorlin syndrome harbouring biallelic CDT1 variants. American Journal of Medical Genetics: Part A. (In Press)

Record type: Article

Abstract

Meier-Gorlin syndrome is an autosomal recessively inherited disorder of growth retardation, accompanied by microtia and patellae a/hypoplasia and characteristic facies. Pathogenic variants in genes associated with the initiation of DNA replication underlie the condition, with biallelic variants in CDT1 the most common cause. Using 10X Chromium genome sequencing, we report CDT1 variants in an adult female, with an inframe amino acid deletion inherited in trans with a deep intronic variant which likely serves as the branchpoint site in intron 8. Splicing defects arising from this variant were confirmed through in vitro analysis. At 49 years, she represents the oldest patient with a molecular diagnosis described in the literature and is the first reported patient with Meier-Gorlin syndrome to have carried a successful pregnancy to term. Both of her pregnancies were complicated by postpartum haemorrhage and upon subsequent necessary hysterectomy, revealed uterine abnormalities. There is scant knowledge on reproductive ability and success in patients with Meier-Gorlin syndrome. Successful pregnancies amongst other clinically recognisable forms of primordial dwarfism have also not been described previously. This case is therefore of clinical interest for many forms of inherited growth retardation, and will assist in providing more information and clinical guidance for females of reproductive age

Text
Successful pregnancies MGORS Bicknell AJMG - Accepted Manuscript
Restricted to Repository staff only until 19 December 2021.
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More information

Accepted/In Press date: 19 December 2020

Identifiers

Local EPrints ID: 446013
URI: http://eprints.soton.ac.uk/id/eprint/446013
ISSN: 1552-4825
PURE UUID: a560e26c-257f-40ed-b7a5-4a70e1459391
ORCID for Karen Temple: ORCID iD orcid.org/0000-0002-6045-1781

Catalogue record

Date deposited: 19 Jan 2021 17:30
Last modified: 18 Feb 2021 16:52

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Contributors

Author: Karen M Knapp
Author: Jennie E. Murray
Author: Karen Temple ORCID iD
Author: Louise S. Bicknell

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