Prenatal Array-CGH Detection of 3q26.32q26.33 Interstitial Deletion Encompassing the SOX2 Gene: Ultrasound, Pathological, and Cytogenetic Findings

Abstract

Background: SOX2 disorders are associated with anophthalmia-esophageal-genital syndrome or microphthalmia, syndromic 3 (MCOPS3- # 206900). Case Report: We describe a third fetal case with a de novo 3q26.32q26.33 deletion extending for 4.31 Mb, detected in a 15-week fetus. After legal interruption of pregnancy, at autopsy, the fetus presented bilateral microphthalmia, right cleft lip and palate, bilateral cerebral ventriculomegaly and dilated third ventricle, microcystic left lung, and intestinal malrotation. Histologically, the left lung showed congenital pulmonary airway malformation (CPAM) type 2. Retinal dysplasia was found in both eyes. Discussion/Conclusion: The human SOX2 gene (OMIM #184429) is located on chromosome 3 at position q26.3–27 and encodes a transcription factor involved in the development of the central and peripheral nervous systems, retina, and lung. In our case, the combination of cerebral, retinal, and pulmonary anomalies, not previously described, are consistent with SOX2 haploinsufficiency due to chromosomal deletion.

Keywords:

• SOX 2 gene
• congenital pulmonary airway malformation type 2
• array comparative genomic hybridization (a-CGH)

Author contributions

M.P.B.: carried out the pathological diagnosis and wrote the manuscript - original draft preparation, review and editing; G.C. and Ma.Pa.: clinically managed the patient; V.B., V.B., M.M., and R.Z.: carried out the genetic diagnosis; Ma.P.o, L.V.: managed the genetic counseling, S.G.C, M.P.B., Ma.Po. and L.G.: revised the manuscript, A.P.: made the histological pictures. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Informed consent statement

The parents signed the consent for publication.

Institutional review board statement

Our investigations were carried out following the rules of the Declaration of Helsinki of 1975, revised in 2013. According to Italian legislation, Ethical Approval for a single case is not required, as long as the data are kept anonymous.

Data availability statement

The data presented in this study are available on request from the corresponding author.

Additional information

Funding

This research received no external funding.