PMC9099044_01
Pedigrees of two families with X-linked hydrocephalus; (A) Pedigree of family 1; (B) Pedigree of family 2; (C) Ultrasound view of the second fetus with severe hydrocephaly from family 2; (D) No hydrocephalus was found in II-3 individual with normal anomaly scan of ultrasound from family 2.
fgene-13-810853-g001.jpg
PMC9099044_01_fgene-13-810853-g001.jpg
F1
A 36-year-old woman was in her second pregnancy at 24 weeks of gestation (Figure 1B). We confirmed hydrocephalus but did not find invisible cavum septum pellucidum by ultrasound (Figure 1C). This healthy female fetus showed a normal anomaly scan of ultrasound in the second trimester (Figure 1D) and was born at 38 weeks of gestation by cesarean section for social reasons.
(A) Exome sequence for the couple from family 1 indicated that the woman was a carrier of the variant (NM_000425: c.1696_1703 + 14del) in the L1CAM gene (red arrows) (B) Exome sequence for family 2 displayed that the deletion of 1511bp in L1CAM chromosome X: 153131395 (hg19/GRCh37)/NM_000425.4:c.2043_2432-121del1511 in the II-2 fetus (green arrows).
fgene-13-810853-g002.jpg
PMC9099044_01_fgene-13-810853-g002.jpg
F2
But trio medical exome sequencing identified a copy number variation in L1CAM inherited from his mother in this male fetus, chromosome X: 153131395-153132905(hg19/GRCh37)/NM_000425.4: c.2043_2432-121del1511 (Figure 2B); this structural variant was confirmed by Sanger sequence (Figure 3B), whereas it has not been previously reported, and it was predicted to cause disruption in partial exon 16 and whole-exons 17 and 18, leading to deletion of fibronectin type-III repeats I-II.
(A) Sanger sequence for the couple from family 1 confirmed that the woman was a carrier of the variant (c.1696_1703 + 14del) in the L1CAM gene. (B) Sanger sequence result for family 2 validated the deletion (c.2043_2432-121del) in L1CAM in II-2 fetus. (C) Agarose gel electrophoresis in the L1CAM result from family 2.
fgene-13-810853-g003.jpg
PMC9099044_01_fgene-13-810853-g003.jpg
F3
But trio medical exome sequencing identified a copy number variation in L1CAM inherited from his mother in this male fetus, chromosome X: 153131395-153132905(hg19/GRCh37)/NM_000425.4: c.2043_2432-121del1511 (Figure 2B); this structural variant was confirmed by Sanger sequence (Figure 3B), whereas it has not been previously reported, and it was predicted to cause disruption in partial exon 16 and whole-exons 17 and 18, leading to deletion of fibronectin type-III repeats I-II. Amniocentesis was performed in our department at 17 weeks of pregnancy, showing and confirming the absence of this mutation (Figure 3C; II-3).