Received: 14 January 2024

DOI: 10.1002/pd.6624

ORIGINAL ARTICLE
- -
Revised: 30 May 2024 Accepted: 3 June 2024

Prenatal exome sequencing for morphologically normal

fetus: Should we be doing it?

Zhi Gao | Xiaofan Zhu | Huanan Ren | Yanfei Wang | Chunxiao Hua |
Xiangdong Kong

Department of Obstetrics and Gynecology,

Genetics and Prenatal Diagnosis Center, The Abstract
First Affiliated Hospital of Zhengzhou
Objective: We aimed to investigate the yield of prenatal exome sequencing (pES) in
University, Zhengzhou, China
morphologically normal fetuses.
Correspondence Method: This retrospective study analyzed 254 families with morphologically
Xiangdong Kong, Director of Genetics and
Prenatal Diagnosis Center, The First Affiliated
normal fetuses who underwent prenatal trio exome sequencing based on parental
Hospital of Zhengzhou University, Zhengzhou request between September 2020 and October 2023.
450000, China.
Email: [email protected]
Results: Overall, abnormal findings were detected in 8 families (3.1%, 8/254) by pES.
Among these, 6 families (2.3%, 6/254) were found to have fetuses affected with
Funding information
monogenic disorders (2 autosomal recessive conditions and 4 autosomal dominant
the Henan Province Medical Science and
Technique Foundation, Grant/Award Number: conditions), while 2 families (0.8%, 2/254) were incidentally found to be couples at
SBGJ202102097; the Henan Province Medical risk of having a future pregnancy with a recessive condition. Among the six fetuses
Science and technology project, Grant/Award
Number: LHGJ20190113 detected with monogenic disorders, two fetuses carried a de novo variant in OPA1
and NF1, which are known to cause Optic atrophy 1 and Neurofibromatosis,
respectively. One fetus was detected with a maternally inherited variant in PKD2
related to polycystic kidney disease 2 (not known to the mother until then). One
fetus was detected with a maternally inherited variant in SDHB associated with
Pheochromocytoma. Two fetuses carried compound heterozygous variants in
NAGLU and GJB2 associated with Mucopolysaccharidosis type IIIB and Deafness,
respectively. In the 2 families where parents were found to be carriers but the
fetuses were unaffected, heterozygous variants in the GJB2 and SERPINB7 genes
were detected in the parents, respectively, which are associated with deafness and
palmoplantar keratoderma.
Conclusion: Our research indicated that pES can provide significant critical infor-
mation for families with morphologically normal fetuses. Prenatal screening with
exome sequencing requires careful management and detailed pre‐test and post‐test
genetic counseling.

Key points
What is already known about this topic?
� Previous studies have demonstrated the increased diagnostic yield and significant clinical
impacts of prenatal exome sequencing (pES) for structurally abnormal fetuses. However,
few studies have published on the yield of pES for morphologically normal fetuses.

Prenatal Diagnosis. 2024;1–7. wileyonlinelibrary.com/journal/pd © 2024 John Wiley & Sons Ltd.

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- GAO ET AL.

What does this study add?

� The yield of pES in morphologically normal fetuses was found to be 3.1%. Prenatal ES can
provide significant critical information for morphologically normal fetuses but detailed pre‐
test and post‐test genetic counseling is necessary.

1 | INTRODUCTION pregnancy. In this study, we reviewed the results of pES in struc-

turally normal fetuses who underwent testing at our center per
It is estimated that as many as 3.5%–5.9% of the worldwide popu- parental request and investigated the yield to offer insights into the
1
lation have a rare disease (RD) and 80% of those are genetic. Some application of pES in the prenatal setting.
genetic disorders causing fetal structural malformations can be
sonographically detected during pregnancy, whereas some cannot.
Chromosomal microarray analysis (CMA), which can detect chro- 2 | SUBJECTS AND METHODS
mosomal aneuploidy and copy number variants (deletions and du-
plications large than 100 kilobase pairs in size), has been primarily 2.1 | Patient population and study design
used for the prenatal diagnosis of fetuses with abnormal morphology,
with a detection rate of 4.9%.2 For pregnancies with normal ultra- This was a retrospective study that included families with morpho-
sound, the prevalence of clinically significant CNVs related to early logically normal fetuses who underwent trio exome sequencing be-
onset disorders is approximately 1.1%, indicating that some genetic tween September 2020 and October 2023. All of these fetuses had
disorders might not be detected by prenatal ultrasound.2 Therefore, exome sequencing due to parental request rather than for medical
CMA is recommended in pregnancies with a structurally normal fetus indications. Prior to performing pES, all fetuses underwent copy
2,3
upon “parental request”. However, genetic disorders caused by number variant sequencing (CNV‐seq), which did not detect any
single nucleotide variants (SNVs) and small insertion/deletions pathogenic or likely pathogenic copy number variants (CNVs). Fam-
(indels) would not be detected by CMA. Exome sequencing (ES), a ilies who had a previous pregnancy affected by a monogenic disease
test with higher resolution compared to CMA, is a potential tool for but the condition in the current fetus had been ruled out though
detecting these genetic diseases. Sanger sequencing or multiplex ligation‐dependent probe amplifica-
In recent years, ES has rapidly evolved in the field of prenatal tion (MLPA) were also included in this study. Fetuses with abnormal
diagnosis of structurally abnormal fetuses with negative karyotype sonographic findings were excluded from this study.
and/or CMA tests, and there is accumulating data supporting the All couples participating in the study were informed about the
clinical utility of prenatal exome sequencing (pES) based on its utility and limitations of pES by experienced clinical geneticists. All
additional diagnostic yield4–9 and significant clinical implications such couples provided written informed consent and consented to the
as prenatal, delivery and neonatal management, recurrence risk report of ACMG secondary findings. The cost of exome sequencing
counseling and reproductive decision‐making.10–15 The International was covered by the patients. This study was approved by the ethical
Society for Prenatal diagnosis (ISPD) recommends pES for pregnan- committee of the First Affiliated Hospital of Zhengzhou University
cies with structurally abnormal fetuses when a genetic etiology is (Ethics No.: 2021‐KY‐0291‐002).
strongly suspected but not for pregnancies without fetal structural
defects, as the fetal phenotype was deemed to be crucial for the
interpretation of genomic variants.16 With the reduction of 2.2 | DNA preparation
sequencing costs and the desire of parents to have a healthy baby,
some pregnant patients without fetal structural defects were Fetal genomic DNA was extracted from chorionic villi sampling (CVS),
inquiring about the use of pES in order to obtain as much information amniotic fluid (AF) and umbilical cord blood and parental genomic
as possible about the future health of the fetus. However, there is DNA was extracted from peripheral blood using the QIAamp DNA
still limited research and data to support the recommendation of pES extraction kit (Qiagen, Germany). Maternal contamination was
in pregnancies with morphologically normal fetuses, and whether excluded by quantitative fluorescent‐polymerase chain reaction.
exome sequencing should be provided for morphologically normal
fetuses has been the subject of great debate.17
At our center, many pregnant patients without fetal structural 2.3 | Exome sequencing and variants analysis
defects have expressed interest in obtaining more information about
their current fetuses through self‐pay pES, especially those who had After the sequencing library was constructed, the whole exons were
a previous pregnancy with a monogenic disease or chromosomal captured using AIExome Human Exome Panel V2 Plus with Target-
abnormality and that condition has been excluded in their current Seq One Hyb & Wash Kit (iGeneTech Co., Ltd) according to the
 10970223, 0, Downloaded from https://obgyn.onlinelibrary.wiley.com/doi/10.1002/pd.6624 by Tufts University, Wiley Online Library on [01/11/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
GAO ET AL.
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manufacturer's instructions and sequenced on the NovaSeq 6000 another genetic disorder. Details of the six families detected with
platform (Illumina) with an average sequencing depth of over 100X fetal monogenic diseases are shown in Table 1 and described below.
and 20X sequencing coverage of at least 98%. Case 1 had a previous child with a deletion involving exons 61–
Sequencing data were analyzed by using Efficient Genosome 62 of the DMD gene. After excluding this variant and chromosomal
Interpretation System (EGIS; Sierra Vast Bio‐Medical, Shanghai, aberrations through MLPA and CNV‐seq, the couple requested pES
China) for mapping, variant calling, and variant annotation. Variant in the current pregnancy to comprehensively assess the risk of ge-
filtering and prioritization were performed based on inheritance netic diseases. A likely pathogenic nonsense variant of PKD2 gene
patterns, literature reports and software pathogenicity estimates. was detected in the fetus by pES, resulting in polycystic kidney dis-
Candidate variants were evaluated using the latest reports in online ease 2 (PKD2), which was confirmed to be inherited from the mother
databases such as ClinVar, DECIPHER, Database of Structural Vari- (condition not known to the mother until then). Following detailed
ations in the Human Genome (DGV), Human Gene Mutation Data- genetic counseling, the couple decided to continue their pregnancy. It
base (HGMD), and Online Mendelian Inheritance in Man (OMIM). was recommended that ultrasonography be performed on the fetal
According to the ACMG guidelines, variants were classified into five kidneys as well as urinary biochemical markers and renal ultrasound
categories: pathogenic (P), likely pathogenic (LP), uncertain signifi- for the mother. Additionally, gene testing was also recommended for
18
cance (VUS), likely benign (LB) and benign (B). other family members.
Prenatal ES results reported were classified into three cate- Case 2 also had a previous pregnancy affected with Duchenne
gories: (1) childhood‐onset disorders: P/LP variants identified in Muscular Dystrophy and the finding in their current pregnancy of a
childhood‐onset disease genes; (2) secondary findings (SFs): P/LP likely pathogenic de novo nonsense variant in OPA1 gene by pES,
19
variants identified in genes on the ACMG recommended list ; (3) which would result in Optic atrophy 1. Autosomal dominant optic
parental carrier status: both parents were carriers for P/LP variants atrophy 1 is characterized by an insidious onset of visual impairment
in the same gene or the mother was a carrier of a P/LP heterozygous in early childhood, leading to moderate to severe loss of visual acuity,
variant in a gene related to X‐linked recessive disorder. All the var- temporal optic disc pallor, color vision deficits, and central scotoma
iants reported were reviewed and discussed on a case‐by‐case basis of variable density. Unfortunately, there is currently no effective
by a multidisciplinary team (MDT) consisting of clinical geneticists, treatment to prevent the development of the disease. After detailed
genetic laboratory specialists, pediatricians and obstetricians. All the genetic counseling, the parents decided to terminate the pregnancy.
reported variants were confirmed by Sanger sequencing. Case 3 had a previous child with Rett syndrome. Compound
heterozygous variants in the NAGLU gene were detected in the fetus:
c.1485_1506dup (p.Asn503Alafs*20) was inherited from the father
3 | RESULTS and c.608G>A (p.Arg203Gln) was inherited from the mother. Both
variants were classified as likely pathogenic according to the ACMG
A total of 254 families with morphologically normal fetuses who variant classification criteria. Variants in the NAGLU gene cause
underwent trio pES due to parental requests were included in this Mucopolysaccharidosis type IIIB, which is characterized by progres-
study. Fetal DNA was extracted from amniotic fluid (74.0%, 188/ sive neurodegeneration, behavioral problems, mild skeletal changes,
254), CVS (25.6%, 65/254) and cord blood (0.4%, 1/254). 227 families and a shortened lifespan. After detailed genetic counseling, the par-
(89.4%, 227/254) opted for pES due to previous pregnancy with a ents decided to terminate the pregnancy.
monogenic disease and the current fetus being found unaffected by Case 4 had a previous pregnancy with a de novo microdeletion of
that condition by Sanger sequencing or MLPA. 18 families (7.1%, 18/ chr22q11.2. In the current fetus, compound heterozygous variants in
254) had normal pregnancy surveillance but opted for pES due to the GJB2 gene were detected: c.235delC(p.Leu79fs) and c.109G>A(p.
family concerns, and 9 families (3.5%, 9/254) opted for pES due to a Val37Ile). Variants in the GJB2 gene are known to be associated with
previous pregnancy with de novo chromosomal disorder. The average AR inherited deafness. The pathogenicity of these two variants was
maternal age was 31.9 years (range: 20–43 years old). The average definite, but there have been multiple accounts of incomplete
gestational age at the time of pES was 18 weeks (range: 13þ4 to penetrance of the latter variant in families or individuals with a
30þ3 weeks) and the average turnaround time (TAT) was 19.1 days biallelic genotype. After detailed genetic counseling, the family made
(range: 9–26 days). All pES results were returned to the patients the decision to continue the pregnancy and had a live birth.
prior to delivery. Case 5 had a previous child with Rett syndrome. A maternally
Overall, abnormal findings were detected in 8 families (3.1%, 8/ inherited missense variant of the SDHB gene was detected in the fetus
254) by pES. Among these, 6 families (2.3%, 6/254) were found to by pES associated with Pheochromocytoma. The mother had a normal
have fetal monogenic diseases (case 1–6), while 2 families (0.8%, 2/ phenotype. After detailed genetic counseling, the couple decided to
254) were incidentally detected as both parents being a carrier of the continue with the pregnancy. Although the phenotype of the mother
same recessive condition (case 7–8). Of the six fetuses with mono- was normal, her risk of developing tumors was still higher than that of
genic disorders, two were autosomal recessive conditions and four the normal population. Thus, the mother was advised to undergo
were autosomal dominant conditions. De novo variants were detec- abdominal ultrasound, chest computed tomography and brain Mag-
ted in two fetuses and both families previously had a pregnancy with netic Resonance Imaging to monitor for pheochromocytoma and
 4
-

TABLE 1 Details of six families detected with fetal monogenic disease.

Fetal findings

Case. Gene Variant (nucleotide, amino ACMG classification Inheritance Pregnancy

no. GA Family history (OMIM) acid change and zygosity) (evidences) mode Disorder Inheritance outcome

Case 18 þ 4 Previous pregnancy with maternally PKD2 NM_000297:c.958C>T(p.Arg320*)het LP(PVS1þPM2_S) AD Polycystic kidney Mat Live birth
1 inherited E61‐62 deletion in DMD (173910) disease 2

Case 18 Previous pregnancy with a de novo OPA1 NM_015560:c.2134C>T(p.Arg712*)het LP(PVS1þPM2_S) AD Optic atrophy 1 de novo Termination
2 E51 deletion in DMD (605290) of pregnancy

Cases 18 Previous pregnancy with Rett NAGLU NM_000263.3:c.1485_1506dup(p. LP(PVS1þPM2)/LP AR Mucopolysaccharidosis pat/mat Termination
3 syndrome (609701) Asn503Alafs*20)het/c.608G>A(p. (PM1þPM2þPM3þPP3) type IIIB of pregnancy
Arg203Gln)het

Cases 18 þ 3 Previous pregnancy with a de novo GJB2 NM_004004:c.109G>A(p.Val37Ile)het/ LP AR Deafness, autosomal pat/mat Live birth
4 microdeletions of chr22q11.2 (121011) c.235delC(p.Leu79fs)het (PM1þPS4þPP1þPM3)/P recessive 1A
(PVS1þPM1þPS4þPS3)

Case 25 Previous pregnancy with Rett SDHB NM_003000:c.137G>A(p.Arg46Gln)het LP AD Pheochromocytoma Mat Live birth
5 syndrome (185470) (PS4þPM1þPM2_SþPP3)

Cases 26þ Previous pregnancy with Cri‐du‐ NF1 NM_000267:c.5546þ1G>T het LP(PVS1þPM2_S) AD Neurofibromatosis de novo Termination
6 chat syndrome (613113) of pregnancy

Abbreviations: ACMG, American College of Medical Genetics and Genomics; AD, autosomal dominant; AR, autosomal recessive; GA, gestational age at testing; het, heterozygous; LP, likely pathogenic; P,
pathogenic; PM, pathogenic moderate; PM2_S, PM2_supporting; PP, pathogenic supporting; PS, pathogenic strong; mat, maternally inherited; pat, paternally inherited.
GAO
ET AL.

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GAO ET AL.
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paraganglioma. Additionally, gene testing was recommended for other normal surveillance, as well as a detection rate of 0.63% (1/160) in
family members. completely normal pregnancies.20 Another large retrospective study
Case 6 had a previous pregnancy with Cri‐du‐chat syndrome. In conducted by Daum et al. included 482 pregnancies and found that
the current fetus, a likely pathogenic de novo splicing region variant the detection rate of pES in structurally normal fetuses was 0.83%.21
of the NF1 gene was detected by pES, which causes Neurofibroma- The detection rate of pES in our study was higher, which may be
tosis. This is an autosomal dominant disorder characterized by cafe‐ related to a different study population. In our study, most of our
au‐lait spots, Lisch nodules in the eye, and fibromatous tumors of the patients had a previous pregnancy with a monogenic and chromo-
skin. Individuals with this disorder have an increased susceptibility to somal disorder. In addition, small study cohorts in our research may
the development of benign and malignant tumors. After detailed influence the results. It is worth noting that in the context of struc-
genetic counseling, the parents opted for pregnancy termination. turally normal fetuses, all P/LP variants can be considered incidental
During the third pregnancy, the family performed prenatal diagnosis and the yield in this study is lower than the detection rate of inci-
of the fetus for this variant and had a healthy newborn. dental findings in previous studies of fetuses with structural mal-
Two families (0.8%, 2/254) were detected with both parents formations. In a systematic review of 72 studies on prenatal ES
being carriers for the same autosomal recessive condition (Table 2, published by Mellis et al., 23 of which reported incidental findings
cases 7 and 8). In case 7, the family had two pregnancies with with a mean yield of 6.3% (129/2062),22 it might suggest that some
chromosomal abnormalities (one was 69, XXY, and the other was monogenic disorders had not yet been associated with prenatal fetal
trisomy‐22), and the current pregnancy had normal CNV‐seq results. structural malformations.
Through exome sequencing, heterozygous variants of the GJB2 gene In this study, the detection rate of monogenic disorders in
were incidentally detected in the parents, which is associated with morphologically normal fetuses was lower than the rate of positive
AR inherited deafness. Fortunately, the current pregnancy did not diagnosis in the fetuses with abnormal morphology.15 However, this
carry the variants. For the next pregnancy, pre‐implantation genetic should not be a reason why pES cannot be used in morphologically
testing for monogenic diseases (PGT‐M) was offered. In case 8, the normal fetuses. A cohort study reviewed the prenatal sonographic
family had a previous pregnancy with compound heterozygous vari- data of 122 patients diagnosed postnatally with a neurocognitive
ants in the SLC45A2 gene, and the current pregnancy did not have disorder using ES and found that 52.5% (64/122) of patients did not
those variants or a chromosomal abnormality had been ruled out for have prenatal sonographic findings.23 This indicates that if prenatal
these variants and chromosomal abnormalities by Sanger sequencing ES is performed solely for the indication of structurally abnormal
and CNV‐seq. Through exome sequencing, the parents were inci- fetuses, some severe monogenic disorders will be missed. In our
dentally detected to be heterozygous variants in the SERPINB7 gene, study, the six fetuses detected with monogenic disorders would not
which results in palmoplantar keratoderma. be expected to present with fetal anomalies (except rarely PKD2) and
these variants would not be screened for by NIPT and CMA.
Furthermore, cases 2 and 6 were found to have a likely pathogenic de
4 | DISCUSSION novo variant in a dominant so would not be detected by expanded
carrier screening. Without pES, these cases would not be diagnosed.
Prenatal ES has primarily been used for the etiological diagnosis of In our study, most families had a previous child with a monogenic
fetuses with fetal structural anomalies and there are few studies disease diagnosed after birth and were under tremendous mental
exploring the value of pES in morphologically normal fetuses. In our and economic pressure. Through pES, the families received valuable
retrospective study, the detection rate of monogenic disorders in information about their current pregnancy in a timely manner,
morphologically normal fetuses was 2.3% (6/254), which is higher providing the basis for genetic counseling for pregnancy decisions
than previously published studies. Vaknin et al. recently conducted a and recurrence risk assessment. In addition, for case 1, the current
study of pES in low‐risk fetuses and found a relatively high detection fetus had a maternally inherited pathogenic variant in the PKD2 gene
rate of 2.86% in low‐risk fetuses with minor ultrasound findings and (not known to the mother until then). Urinary biochemical markers

TABLE 2 Details of two families detected with both parents being carriers for the same autosomal recessive condition.

Case. Gene Variant (nucleotide, amino ACMG Inheritance

no. (OMIM) Transcript ID acid change and zygosity) classification mode Disorder Inheritance

Case 7 GJB2 (121011) NM_004004 c.299_300delAT P AR Deafness, autosomal recessive 1A Mat

(p.His100fs)het

c.235delC(p.Leu79fs)het P Pat

Case 8 SERPINB7 NM_001261830 c.796C>T(p.Arg266*)het P AR Palmoplantar keratoderma, Mat

(603357) Nagashima type
c.522dupT(p.Val175fs)het LP Pat

Abbreviations: ACMG, American College of Medical Genetics and Genomics; AR, autosomal recessive; het, heterozygous; mat, maternally inherited; pat,
paternally inherited; LP, likely pathogenic; P, pathogenic.
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6
- GAO ET AL.

and a renal ultrasound of the mother were recommended. If neces- 5 | CONCLUSION

sary, early treatment could be promptly carried out. In case 5, the
current fetus had a maternally inherited pathogenic variant in the In conclusion, our study demonstrated a significant yield of pES in
SDHB gene linked to Pheochromocytoma. Although the mother's morphologically normal fetuses. Given the limitations of exome
phenotype was normal, the risk of developing tumors was still higher sequencing, it is essential to provide careful management and
than the general population and recommendations were made for the detailed pre‐test and post‐test genetic counseling is necessary when
mother to undergo abdominal ultrasound, chest computed tomog- conducting pES on morphologically normal fetuses.
raphy, and brain Magnetic Resonance Imaging to monitor pheo-
chromocytoma and paraganglioma. In such cases, a clear benefit AC K NO W L ED G M E NT S
could be obtained for the fetus and the transmitting parent. Four We are grateful to the families for consenting and participating in this
families were detected with both parents being carriers for the same study. We greatly appreciate the support from a multidisciplinary
autosomal recessive condition (cases 3, 4, 7 and 8), resulting in a yield team of clinical geneticists, genetic laboratory specialists, pediatri-
of 1.6% (4/254). An exome‐based carrier‐screening program for cians and obstetricians at the First Affiliated Hospital of Zhengzhou
recessive disorders would have revealed the parental carrier status. University. This work was supported by the Henan Province Medical
This underscores the significance of conducting an expanded carrier‐ Science and technology project (joint construction) (LHGJ20190113)
screening test for couples looking to reduce the risk of having an and the Henan Province Medical Science and Technique Foundation
affected child.24 (SBGJ202102097).
Although pES is powerful, it does not detect all types of variants.
For example, it cannot detect variants in deep intron regions, accu- CO N F L I C T O F I NT E RE S T S T A T E M E NT
rately analyze repeat expansion variants, areas with high GC content, The authors declare no conflicts of interest.
and small (one or two) exon deletions.25 In addition to the technical
limitations, another challenge is the interpretation of variants. The DATA AVAILABILITY STATEMENT
lack of fetal phenotypic information makes it difficult to analyze The data that support the findings of this study are available on
genome data and provide genetic counseling. Considerable resources request from the corresponding author. The data are not publicly
are required to review the large dataset to find potentially patho- available due to privacy or ethical restrictions.
genic variants in the absence of fetal phenotypic information. In
addition, some monogenic disorders may have incomplete pene- ET H I C S S T A T E M EN T
trance and variable expression, making it difficult, despite genetic This study was approved by the Research Ethics Committee (REC) of
counseling, to decide about termination of pregnancy. Therefore, the First Affiliated Hospital of Zhengzhou University (Ethics No.:
detailed pre‐test and post‐test genetic counseling is necessary. Pa- 2021‐KY‐0291‐002). Subjects provided written informed consent
tients should be informed that a negative exome sequencing result approved by the REC of the First Affiliated Hospital of Zhengzhou
does not completely rule out the presence of a genetic disease in the University.
fetus and that pathogenic genetic variants do not always guarantee
the development of the disease. ORCID
The reporting scope of prenatal exome sequencing presents a Zhi Gao https://orcid.org/0000-0002-1898-5309
significant challenge, as there are currently no guidelines in place to Yanfei Wang https://orcid.org/0000-0002-3643-6311
define the reporting scope. Gold NB et al. suggested that an entirely Xiangdong Kong https://orcid.org/0000-0003-0030-7638
new list of “prenatal actionable findings” should be offered alongside
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Prenatal Diagnosis 2022 debate 3‐Fetal genome sequencing should