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Prenatal ultrasound phenotypic and genetic etiology of the 17q12 microduplication syndrome - PubMed

  • ️Sat Jan 01 2022

Prenatal ultrasound phenotypic and genetic etiology of the 17q12 microduplication syndrome

Meiying Cai et al. Front Pediatr. 2022.

Abstract

Background: Several studies have reported on the clinical phenotype of the 17q12 microduplication syndrome, a rare autosomal dominant genetic disorder, in children and adults, but few have reported on its prenatal diagnosis. This study analyzed the prenatal ultrasound phenotypes of the 17q12 microduplication syndrome to improve the understanding, diagnosis, and monitoring of this disease in fetuses.

Methods: A retrospective analysis of 8,200 pregnant women who had received an invasive antenatal diagnosis at tertiary referral hospitals between January 2016 and August 2021 was performed. Amniotic fluid or cord blood was sampled from the pregnant women for karyotyping and chromosome microarray analysis (CMA).

Results: The CMA revealed microduplication in the 17q12 region of the genome in five fetuses, involving fragments of about 1.5-1.9 Mb. Five fetuses with the 17q12 microduplication syndrome had different prenatal ultrasound phenotypes, including duodenal obstruction (two fetuses); mild ventriculomegaly, dysplasia of the septum pellucidum, agenesis of the corpus callosum (one fetus); and a strong echo in the left ventricle only (one fetus). The ultrasound phenotype of one fetus was normal. Among the five fetuses with the 17q12 microduplication syndrome, the parents of three refused CNV segregation analysis, while CNV segregation analysis was performed for the remaining two fetuses to confirm whether the disorder was inherited maternally or paternally, with normal phenotypes. After genetic counseling, the parents of those two fetuses chose to terminate the pregnancy, while the parents of the three unverified fetuses continued the pregnancy, with normal follow-up after birth.

Conclusion: Although prenatal ultrasound phenotypes in fetuses with the 17q12 microduplication syndrome are highly variable, our study has highlighted the distinct association between duodenal obstruction and the 17q12 microduplication syndrome. Understanding the relationship between the pathogenesis of the 17q12 microduplication in prenatal ultrasound phenotypes and its long-term prognosis will contribute to better genetic counseling concerning the 17q12 microduplication syndrome, which is still a challenge.

Keywords: 17q12 microduplication syndrome; chromosome microarray analysis; duodenal obstruction; fetal ultrasound phenotype; pregnancy outcome.

Copyright © 2022 Cai, Lin, Guo, Fu, Xu, Lin and Huang.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1

The prenatal ultrasound phenotype of the fetuses. (A) Showed duodenal obstruction. (B) Showed mild ventriculomegaly, dysplasia of the septum pellucidum, agenesis of the corpus callosum. (C) Showed a strong echo in the left ventricle.

FIGURE 2
FIGURE 2

CMA revealed microduplication in the 17q12 region of the genome in five fetuses, involving fragment size about 1.5–1.9 Mb, including HNF1B (189907), LHX1 (601999), CCL4L1 (603782), CCL4L2 (610757), CCL3L1 (601395), and 15 other OMIM genes.

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References

    1. Rasmussen M, Vestergaard EM, Graakjaer J, Petkov Y, Bache I, Fagerberg C, et al. 17q12 deletion and duplication syndrome in Denmark-a clinical cohort of 38 patients and review of the literature. Am J Med Genet A. (2016) 170:2934–42. 10.1002/ajmg.a.37848 - DOI - PubMed
    1. Mefford HC, Sharp AJ, Pinkel D, Ventura M, Moller RS, Ullmann R, et al. Recurrent reciprocal genomic Rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. Am J Hum Genet. (2013) 81:1057–69. - PMC - PubMed
    1. Nagamani S, Erez A, Shen J, Li C, Roeder E, Cox S, et al. Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12. Eur J Hum Genet. (2010) 18:278–84. 10.1038/ejhg.2009.174 - DOI - PMC - PubMed
    1. Bierhals T, Maddukuri SB, Kutsche K, Girisha KM. Expanding the phenotype associated with 17q12 duplication: case report and review of the literature. Am J Med Genet A. (2013) 161A:352–9. 10.1002/ajmg.a.35730 - DOI - PubMed
    1. Battini R. 17q12 recurrent deletions and duplications: description of a case series with neuropsychiatric phenotype. Genes. (2021) 12:1660. 10.3390/genes12111660 - DOI - PMC - PubMed