Figure - available from: Clinical Case Reports
This content is subject to copyright. Terms and conditions apply.
A, De novo c.1109G>A p.(Cys370Tyr) variant in exon 2 of the ZIC2 gene visualized in IGV. B, Presence of the mutation in the fetus but none of the parent was confirmed by Sanger sequencing. C, Schematic representation of the ZIC2 gene and its protein (with the main protein domains) along with the mutation described in MIHV until now (data collected from Ref.14,15). Our missense mutation is shown in red
Source publication
We present a case of a middle interhemispheric variant of antenatal discovery associated with a de novo missense variant (NM_007129.5: c.1109G>A p.(Cys370Tyr)) in the ZIC2 gene. Our case represents the first prenatal description of a ZIC2 missense mutation found in association with syntelencephaly. We present a case of a middle interhemispheric var...
Citations
... confirmó la deleción y las regiones afectadas (Tabla 2). Recientemente, una asociación a mutación del gen ZIC2 ha sido descrita asociada a sintelencefalia 28 . Con relación a la evolución a más largo plazo, el caso 1 (diagnóstico año 2012) tuvo seguimiento hasta los 3 años de vida; los casos 4 y 5 cumplieron 6 meses de vida al momento de redactar este manuscrito. ...
Introducción y objetivo:
Demostrar el valor del plano axial del complejo posterior, como apoyo a la detección antenatal de sintelencefalia, variante de holoprosencefalia.
Método:
Se incluyeron todas las pacientes con diagnóstico de sintelencefalia evaluadas desde el año 2008. En todos los casos se consignaron los datos clínicos, de neurosonografía (NSG), de resonancia magnética (RM) y genética.
Resultados:
Cuatro casos fueron diagnosticados en el segundo trimestre y en todos se realizó estudio genético y RM. Tres tuvieron en su evolución anomalías extra-SNC y dos de ellos alteraciones cromosómicas, una de ellas incompatible con la vida extrauterina. Lo hallazgos descritos en neuroimagen para esta afección fueron detectados en la NSG, con una excelente correlación con RM, ya fuera esta última realizada en periodo fetal o posnatal.
Conclusión:
El diagnóstico prenatal de variantes de holoprosencefalia es difícil, considerando la existencia de una fusión medial más acotada que en las formas clásicas. El presente estudio demuestra la utilidad del plano del complejo posterior para la sospecha diagnóstica de sintelencefalia.
(Abstracted from Genet Med 2022;24:344–363)
Approximately 2% to 3% of pregnancies are affected by fetal abnormalities, and many of these are detected by ultrasound. After identification of suspected fetal structural anomaly, invasive procedures such as chorionic villus sampling and amniocentesis are offered as a method of prenatal genetic diagnosis.
Purpose
We compared the diagnostic yield of fetal clinical exome sequencing (fCES) in prospective and retrospective cohorts of pregnancies presenting with anomalies detected using ultrasound. We evaluated factors that led to a higher diagnostic efficiency, such as phenotypic category, clinical characterization, and variant analysis strategy.
Methods
fCES was performed for 303 fetuses (183 ongoing and 120 ended pregnancies, in which chromosomal abnormalities had been excluded) using a trio/duo-based approach and a multistep variant analysis strategy.
Results
fCES identified the underlying genetic cause in 13% (24/183) of prospective and 29% (35/120) of retrospective cases. In both cohorts, recessive heterozygous compound genotypes were not rare, and trio and simplex variant analysis strategies were complementary to achieve the highest possible diagnostic rate. Limited prenatal phenotypic information led to interpretation challenges. In 2 prospective cases, in-depth analysis allowed expansion of the spectrum of prenatal presentations for genetic syndromes associated with the SLC17A5 and CHAMP1 genes.
Conclusion
fCES is diagnostically efficient in fetuses presenting with cerebral, skeletal, urinary, or multiple anomalies. The comparison between the 2 cohorts highlights the importance of providing detailed phenotypic information for better interpretation and prenatal reporting of genetic variants.
