OC20.02: Prenatal diagnosis by chromosome microarray analysis and whole-exome sequencing for fetuses with skeletal dysplasia

Abstract Background Osteocraniostenosis (OCS) is a rare genetic disorder characterised by premature closure of cranial sutures, gracile bones and perinatal lethality. Previously, diagnosis has only been possible postnatally on clinical and radiological features. This study describes the first prenatal diagnosis of OCS. Case presentation In this case prenatal ultrasound images were suggestive of a serious but non-lethal skeletal dysplasia. Due to the uncertain prognosis the parents were offered Whole Exome Sequencing (WES), which identified a specific gene mutation in the FAMIIIa gene. This mutation had previously been detected in two cases and was lethal in both perinatally. This established the diagnosis, a clear prognosis and allowed informed parental choice regarding ongoing pregnancy management. Conclusions This case report supports the use of targeted WES prenatally to confirm the underlying cause and prognosis of sonographically suspected abnormalities.

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Prenatal Diagnosis and Prognosis of Fetal Hyperechogenic Kidney: A Study of 80 Cases

10.21203/rs.3.rs-689734/v1 ◽

2021 ◽

Author(s):

Jin HAN ◽

YanJun Huang ◽

Bing Ji ◽

Zequn liu ◽

Shuzheng Xu ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Microarray Analysis ◽

Karyotype Analysis ◽

Single Gene ◽

Detection Methods ◽

Genetic Characteristics ◽

Whole Exome ◽

Chromosome Karyotype

Abstract Background Prenatal diagnosis of fetal hyperechogenic kidney poses a challenge. The aim of this study was to investigate the genetic reasons and prognosis of fetal hyperechogenic kidney diagnosed on prenatal ultrasonography. Methods We retrospectively reviewed the clinical data of 80 cases of prenatally diagnosed fetal hyperechogenic kidney by the obstetric ultrasound. The genetic characteristics and pregnancy outcomes were analyzed using chromosome karyotype analysis, chromosome microarray analysis, and whole-exome sequencing. Results Of the 80 cases, 48 (60%) were those of isolated fetal hyperechogenic kidney and 32 (40%) were those of non-isolated cases, including 4 cases (5%) of urinary system abnormalities, 7 (8.75%) of central nervous system abnormalities, 5 (6.25%) of cardiac abnormalities, and 16 (20%) of multiple abnormalities. Chromosome karyotype analysis and microarray analysis revealed 17 (21.25%) abnormalities, including isolated fetal hyperechogenic kidney (9, 11.25%) and chromosome microdeletion microduplication (17q12 microdeletion syndrome, Williams-Beuren syndrome, 4p16.3-p16.1 microduplication syndrome) (8, 10%). Moreover, 9 patients had single gene mutations, including those of BBS2, BBS7, HNF1B, ACE, CEP290, COL4A5, and PKHD1. Total 48 pregnancies were terminated (57.3%), and the remaining 32 fetuses survived and grew normally, the neonatal renal function tests were normal. Conclusions Fetal hyperechogenic kidney chromosome abnormalities are common, in particular, there is considerable prevalence of isolated fetal hyperechogenic kidney. Therefore, advances in prenatal diagnosis are crucial, if necessary, with the combined use of whole-exome sequencing and other comprehensive detection methods.

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