Genetic analyses in small for gestational age newborns
Genetic analyses in small for gestational age newborns
Context: Small for gestational age (SGA) can be a result of fetal growth restriction, associated with perinatal morbidity and mortality. Mechanisms that control prenatal growth are poorly understood.
Objective: The aim of the present study was to gain more insight into prenatal growth failure and determine an effective diagnostic approach in SGA newborns. We hypothesized that one or more CNVs and disturbed methylation and sequence variants may be present in genes known to be associated with fetal growth.
Design: A prospective cohort study of subjects with a low birthweight for gestational age.
Setting: The study was conducted at an academic pediatric research institute.
Patients: A total of 21 SGA newborns with a mean birthweight below the 1st centile and a control cohort of 24 appropriate for gestational age newborns were studied.
Intervention: Array comparative genomic hybridization, genome-wide methylation studies and exome sequencing were performed.
Main Outcome Measures: The numbers of copy number variations, methylation disturbances and sequence variants.
Results: The genetic analyses demonstrated three CNVs, one systematically disturbed methylation pattern and one sequence variant explaining the SGA. Additional methylation disturbances and sequence variants were present 20 patients. In 19 patients, multiple abnormalities were found.
Conclusion: Our results confirm the influence of a large number of mechanisms explaining dysregulation of fetal growth. We conclude that copy number variations, methylation disturbances and sequence variants all contribute to prenatal growth failure. Such genetic workup can be an effective diagnostic approach in SGA newborns.
Journal Article
917-925
Stalman, Susanne E.
5639d909-84f1-4573-88d0-2a7835b994b0
Solanky, Nita
7dbb6851-bd3c-4150-8193-6876275594b5
Ishida, Miho
615e5c2d-ea24-42a0-8b8b-c3711c6435a6
Alemán-Charlet, Cristina
62e9f8ff-4e26-44f6-a7d5-52b0b37762d3
Abu-Amero, Sayeda
5f53d63f-f2e1-4c89-920c-1ff1cfcfc9a6
Alders, Marielle
bb9f98b8-4d54-40ba-9d69-1e17008bb599
Alvizi, Lucas
97093e74-9195-4099-9114-94b40b23b661
Baird, William
59891557-bb83-4013-b326-35f250c6a790
Demetriou, Charalambos
4e227e4a-4494-4489-8fd0-831734d85d0f
Henneman, Peter
723bffa8-5899-445a-9958-09a01f452992
James, Chela
44e13e6d-5a06-40eb-9419-0bf0991cde85
Knegt, Lia C.
ec0f34d8-07dd-4f83-8a0e-be72ee7b5f94
Leon, Lydia J.
8eaa8fd5-c860-4288-8e2a-73074f8eed6c
Mannens, Marcel M.A.M.
bb288561-4e69-4243-956b-894269170cd1
Mul, Adi N.
03a504df-4aa4-4219-b5e4-b518abe22f55
Nibbering, Nicole A.
5104d0c9-10c9-4f88-9b78-985f11c0b63e
Peskett, Emma
fcce1e7d-9977-4dcb-9bbd-767a9d1baf64
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Ris-Stalpers, Carrie
9dc4f81a-35fc-44a7-b980-5cd2cfba31fe
van der Post, Joris A.M.
8ea51a27-2fb3-4831-988b-1f49bd6fad1b
Kamp, Gerdine A.
4e89f63b-d406-4764-9513-06ca61312390
Plötz, Frans B.
1d90731b-35a6-42b7-bffc-2c3167987e5d
Wit, Jan M.
37490622-56fb-4a4a-8122-ee40cec1f446
Stanier, Philip
20df9ad5-7153-4e45-98f7-b265e15980c7
Moore, Gudrun E.
d071953a-3ee2-4b6d-80a0-3ddfca274e15
Hennekam, Raoul C.
85ba9cf8-c151-4473-aca8-25b90b33fd3b
March 2018
Stalman, Susanne E.
5639d909-84f1-4573-88d0-2a7835b994b0
Solanky, Nita
7dbb6851-bd3c-4150-8193-6876275594b5
Ishida, Miho
615e5c2d-ea24-42a0-8b8b-c3711c6435a6
Alemán-Charlet, Cristina
62e9f8ff-4e26-44f6-a7d5-52b0b37762d3
Abu-Amero, Sayeda
5f53d63f-f2e1-4c89-920c-1ff1cfcfc9a6
Alders, Marielle
bb9f98b8-4d54-40ba-9d69-1e17008bb599
Alvizi, Lucas
97093e74-9195-4099-9114-94b40b23b661
Baird, William
59891557-bb83-4013-b326-35f250c6a790
Demetriou, Charalambos
4e227e4a-4494-4489-8fd0-831734d85d0f
Henneman, Peter
723bffa8-5899-445a-9958-09a01f452992
James, Chela
44e13e6d-5a06-40eb-9419-0bf0991cde85
Knegt, Lia C.
ec0f34d8-07dd-4f83-8a0e-be72ee7b5f94
Leon, Lydia J.
8eaa8fd5-c860-4288-8e2a-73074f8eed6c
Mannens, Marcel M.A.M.
bb288561-4e69-4243-956b-894269170cd1
Mul, Adi N.
03a504df-4aa4-4219-b5e4-b518abe22f55
Nibbering, Nicole A.
5104d0c9-10c9-4f88-9b78-985f11c0b63e
Peskett, Emma
fcce1e7d-9977-4dcb-9bbd-767a9d1baf64
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Ris-Stalpers, Carrie
9dc4f81a-35fc-44a7-b980-5cd2cfba31fe
van der Post, Joris A.M.
8ea51a27-2fb3-4831-988b-1f49bd6fad1b
Kamp, Gerdine A.
4e89f63b-d406-4764-9513-06ca61312390
Plötz, Frans B.
1d90731b-35a6-42b7-bffc-2c3167987e5d
Wit, Jan M.
37490622-56fb-4a4a-8122-ee40cec1f446
Stanier, Philip
20df9ad5-7153-4e45-98f7-b265e15980c7
Moore, Gudrun E.
d071953a-3ee2-4b6d-80a0-3ddfca274e15
Hennekam, Raoul C.
85ba9cf8-c151-4473-aca8-25b90b33fd3b
Stalman, Susanne E., Solanky, Nita, Ishida, Miho, Alemán-Charlet, Cristina, Abu-Amero, Sayeda, Alders, Marielle, Alvizi, Lucas, Baird, William, Demetriou, Charalambos, Henneman, Peter, James, Chela, Knegt, Lia C., Leon, Lydia J., Mannens, Marcel M.A.M., Mul, Adi N., Nibbering, Nicole A., Peskett, Emma, Rezwan, Faisal I., Ris-Stalpers, Carrie, van der Post, Joris A.M., Kamp, Gerdine A., Plötz, Frans B., Wit, Jan M., Stanier, Philip, Moore, Gudrun E. and Hennekam, Raoul C.
(2018)
Genetic analyses in small for gestational age newborns.
Journal of Clinical Endocrinology & Metabolism, 3 (1), .
(doi:10.1210/jc.2017-01843).
Abstract
Context: Small for gestational age (SGA) can be a result of fetal growth restriction, associated with perinatal morbidity and mortality. Mechanisms that control prenatal growth are poorly understood.
Objective: The aim of the present study was to gain more insight into prenatal growth failure and determine an effective diagnostic approach in SGA newborns. We hypothesized that one or more CNVs and disturbed methylation and sequence variants may be present in genes known to be associated with fetal growth.
Design: A prospective cohort study of subjects with a low birthweight for gestational age.
Setting: The study was conducted at an academic pediatric research institute.
Patients: A total of 21 SGA newborns with a mean birthweight below the 1st centile and a control cohort of 24 appropriate for gestational age newborns were studied.
Intervention: Array comparative genomic hybridization, genome-wide methylation studies and exome sequencing were performed.
Main Outcome Measures: The numbers of copy number variations, methylation disturbances and sequence variants.
Results: The genetic analyses demonstrated three CNVs, one systematically disturbed methylation pattern and one sequence variant explaining the SGA. Additional methylation disturbances and sequence variants were present 20 patients. In 19 patients, multiple abnormalities were found.
Conclusion: Our results confirm the influence of a large number of mechanisms explaining dysregulation of fetal growth. We conclude that copy number variations, methylation disturbances and sequence variants all contribute to prenatal growth failure. Such genetic workup can be an effective diagnostic approach in SGA newborns.
Text
jc.2017-01843
- Version of Record
Restricted to Repository staff only
Request a copy
More information
Accepted/In Press date: 9 January 2018
e-pub ahead of print date: 12 January 2018
Published date: March 2018
Keywords:
Journal Article
Identifiers
Local EPrints ID: 419820
URI: http://eprints.soton.ac.uk/id/eprint/419820
ISSN: 0021-972X
PURE UUID: b5a9e15b-ddb9-4d7c-ab21-1b6bbdecf40c
Catalogue record
Date deposited: 20 Apr 2018 16:31
Last modified: 16 Mar 2024 04:13
Export record
Altmetrics
Contributors
Author:
Susanne E. Stalman
Author:
Nita Solanky
Author:
Miho Ishida
Author:
Cristina Alemán-Charlet
Author:
Sayeda Abu-Amero
Author:
Marielle Alders
Author:
Lucas Alvizi
Author:
William Baird
Author:
Charalambos Demetriou
Author:
Peter Henneman
Author:
Chela James
Author:
Lia C. Knegt
Author:
Lydia J. Leon
Author:
Marcel M.A.M. Mannens
Author:
Adi N. Mul
Author:
Nicole A. Nibbering
Author:
Emma Peskett
Author:
Faisal I. Rezwan
Author:
Carrie Ris-Stalpers
Author:
Joris A.M. van der Post
Author:
Gerdine A. Kamp
Author:
Frans B. Plötz
Author:
Jan M. Wit
Author:
Philip Stanier
Author:
Gudrun E. Moore
Author:
Raoul C. Hennekam
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics