TY - JOUR
T1 - Genetic Analyses in Small for Gestational Age Newborns
AU - Stalman, Susanne E.
AU - Solanky, Nita
AU - Ishida, Miho
AU - Alemán-Charlet, Cristina
AU - Abu-Amero, Sayeda
AU - Alders, Marielle
AU - Alvizi, Lucas
AU - Baird, William
AU - Demetriou, Charalambos
AU - Henneman, Peter
AU - James, Chela
AU - Knegt, Lia C.
AU - Leon, Lydia J.
AU - Mannens, Marcel M. A. M.
AU - Mul, Adi N.
AU - Nibbering, Nicole A.
AU - Peskett, Emma
AU - Rezwan, Faisal I.
AU - Ris-Stalpers, Carrie
AU - van der Post, Joris A. M.
AU - Kamp, Gerdine A.
AU - Plötz, Frans B.
AU - Wit, Jan M.
AU - Stanier, Philip
AU - Moore, Gudrun E.
AU - Hennekam, Raoul C.
PY - 2018
Y1 - 2018
N2 - 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. 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. A prospective cohort study of subjects with a low birthweight for gestational age. The study was conducted at an academic pediatric research institute. 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. Array comparative genomic hybridization, genome-wide methylation studies and exome sequencing were performed. The numbers of copy number variations, methylation disturbances and sequence variants. 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. 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
AB - 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. 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. A prospective cohort study of subjects with a low birthweight for gestational age. The study was conducted at an academic pediatric research institute. 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. Array comparative genomic hybridization, genome-wide methylation studies and exome sequencing were performed. The numbers of copy number variations, methylation disturbances and sequence variants. 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. 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
U2 - https://doi.org/10.1210/jc.2017-01843
DO - https://doi.org/10.1210/jc.2017-01843
M3 - Article
C2 - 29342293
SN - 0021-972X
VL - 103
SP - 917
EP - 925
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 3
ER -