Context: Small for gestational age (SGA) can be the result of fetal growth restriction, which is associated with perinatal morbidity and mortality. Mechanisms that control prenatal growth are poorly understood. Objective: The aim of the current 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 copy number variations (CNVs) and disturbed methylation and sequence variants may be present in genes associated with fetal growth. Design: A prospective cohort study of subjects with a low birth weight for gestational age. Setting: The study was conducted at an academic pediatric research institute. Patients: A total of 21 SGA newborns with a mean birth weight below the first centile and a control cohort of 24 appropriate-for-gestational-age newborns were studied. Interventions: Array comparative genomic hybridization, genome-wide methylation studies, and exome sequencing were performed. Main Outcome Measures: The numbers of CNVs, methylation disturbances, and sequence variants. Results: The genetic analyses demonstrated three CNVs, one systematically disturbed methylation pattern, and one sequence variant explaining SGA. Additional methylation disturbances and sequence variants were present in 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 concluded that CNVs, methylation disturbances, and sequence variants all contribute to prenatal growth failure. These genetic workups can be an effective diagnostic approach in SGA newborns.
Context: Small for gestational age (SGA) can be the result of fetal growth restriction, which is associated with perinatal morbidity and mortality. Mechanisms that control prenatal growth are poorly understood. Objective: The aim of the current 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 copy number variations (CNVs) and disturbed methylation and sequence variants may be present in genes associated with fetal growth. Design: A prospective cohort study of subjects with a low birth weight for gestational age. Setting: The study was conducted at an academic pediatric research institute. Patients: A total of 21 SGA newborns with a mean birth weight below the first centile and a control cohort of 24 appropriate-for-gestational-age newborns were studied. Interventions: Array comparative genomic hybridization, genome-wide methylation studies, and exome sequencing were performed. Main Outcome Measures: The numbers of CNVs, methylation disturbances, and sequence variants. Results: The genetic analyses demonstrated three CNVs, one systematically disturbed methylation pattern, and one sequence variant explaining SGA. Additional methylation disturbances and sequence variants were present in 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 concluded that CNVs, methylation disturbances, and sequence variants all contribute to prenatal growth failure. These genetic workups can be an effective diagnostic approach in SGA newborns.
Authors: Hwal Rim Jeong; Jae-A Han; Heeji Kim; Hye Jin Lee; Young Suk Shim; Min Jae Kang; Jong Seo Yoon; Seongho Ryu; Il Tae Hwang Journal: Genes (Basel) Date: 2022-05-24 Impact factor: 4.141
Authors: Paula Ocaranza; Monique Losekoot; Marie J. E. Walenkamp; Christiaan De Bruin; Jan M. Wit; Veronica Mericq Journal: J Clin Res Pediatr Endocrinol Date: 2019-03-12
Authors: E Inzaghi; A Deodati; S Loddo; M Mucciolo; F Verdecchia; E Sallicandro; G Catino; M Cappa; A Novelli; S Cianfarani Journal: J Endocrinol Invest Date: 2021-07-13 Impact factor: 4.256
Authors: Claudia Gundacker; Klaudia Graf-Rohrmeister; Martin Gencik; Markus Hengstschläger; Karol Holoman; Petra Rosa; Renate Kroismayr; Ivo Offenthaler; Veronika Plichta; Theresa Reischer; Isabella Teufl; Wolfgang Raffesberg; Sigrid Scharf; Birgit Köhler-Vallant; Zoja Delissen; Stefan Weiß; Maria Uhl Journal: Front Genet Date: 2021-06-16 Impact factor: 4.599