Molecular analysis of 31 cases with fetal skeletal dysplasia
Author:
Taşdemir Ümit1ORCID, Eyisoy Ömer Gökhan1ORCID, Gezer Murad1, Karaman Ali2, Demirci Oya1
Affiliation:
1. Department of Obstetrics, Division of Perinatology , Zeynep Kamil Women and Children Diseases Education and Research Hospital , Istanbul , Türkiye 2. Department of Genetics , Zeynep Kamil Women and Children Diseases Education and Research Hospital , Istanbul , Türkiye
Abstract
Abstract
Objectives
The aim of this study was to describe the prenatal ultrasound findings of fetuses with skeletal dysplasia and to evaluate the genetic variations by molecular genetic analysis.
Methods
Between August 1, 2018 and March 1, 2023, we conducted a retrospective case series at a tertiary referral center involving patients with fetal skeletal abnormalities. For cases referred for a possible diagnosis of fetal skeletal dysplasia, an ultrasound database and prenatal genetic counseling records were first searched. Terminated cases diagnosed with skeletal dysplasia by pathologic and radiologic findings and cases with skeletal dysplasia proven by postnatal clinical findings were included in the study.
Results
Between 2018 and 2023, a total of 64 cases were diagnosed as skeletal dysplasia based on radiologic findings, pathologic findings, and clinical features. The median week of the first ultrasound performed on patients is 19 0/7 weeks, while the median week of the ultrasound in which skeletal dysplasia is suspected is 21 3/7 weeks. Although micromelia was evaluated as a common feature in all cases, the most common concomitant anomaly was thoracic hypoplasia. Exome sequencing analysis was achieved in 31 (48 %) of cases. In 31 cases, in total of 35 pathogenic single gene mutations and 5 VUS (variants of uncertain significance) variants composing of 23 autosomal dominant, 10 autosomal recessive and 2 X linked recessive mutations were determined.
Conclusions
Prenatal ultrasound findings can lead us to specific diagnoses, and with the appropriate molecular analysis method, a definitive diagnosis can be made without wasting time and money.
Publisher
Walter de Gruyter GmbH
Reference11 articles.
1. Dighe, M, Fligner, C, Cheng, E, Warren, B, Dubinsky, T. Fetal skeletal dysplasia: an approach to diagnosis with illustrative cases. Radiographics 2008;28:1061–77. https://doi.org/10.1148/rg.284075122. 2. Orioli, I, Castilla, E, Barbosa-Neto, J. The birth prevalence rates for the skeletal dysplasias. J Med Genet 1986;23:328–32. https://doi.org/10.1136/jmg.23.4.328. 3. Mortier, GR, Cohn, DH, Coormier-Daire, V, Hall, C, Krakow, D, Mundlos, S, et al.. Nosology and classification of genetic skeletal disorders: 2019 revision. Am J Med Genet Part A 2019;179:2393–419. https://doi.org/10.1002/ajmg.a.61366. 4. Geister, KA, Camper, SA. Advances in skeletal dysplasia genetics. Annu Rev Genomics Hum Genet 2015;16:199–227. https://doi.org/10.1146/annurev-genom-090314-045904. 5. Yang, K, Shen, M, Yan, Y, Tan, Y, Zhang, J, Wu, J, et al.. Genetic analysis in fetal skeletal dysplasias by trio whole-exome sequencing. BioMed Res Int 2019;14:1–8. https://doi.org/10.1155/2019/2492590.
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