Online first
Research paper
Published online: 2023-04-26

open access

Page views 423
Article views/downloads 358
Get Citation

Connect on Social Media

Connect on Social Media

Prenatal detection of chromosomal abnormalities and copy number variants in fetuses with corpus callosum agenesis

zheng jiao1, Tingting Song, Ying Xu, Jia Li, Pengfei Liu, Jiangfang Zhang, Hong Yang

Abstract

Objectives: The corpus callosum is the main pathway that connects interhemispheric communication. Agenesis of corpus callosum (ACC) have not consistently detected replicate genetic risk factors, potentially due to Etiological heterogeneity of this trait. This study aimed to retrospectively analyze the molecular basis for the ACC and the potential genotyping-phenotyping association and provide the basis for genetic counselling.

Material and methods: Karyotyping and chromosomal microarray analysis were performed for copy number variants.

Results: Three cases had 1p36 deletions, two cases had 2q31.2 and 2p16.3 microdeletions, one case had microdeletion of Xq26.3q27.1, five cases involved derived chromosomes due to unbalanced translocations. These cases had variable deletions and duplications with partial overlapping. Phenotypically, besides agenesis of corpus callosum and other brain morphological abnormalities as well as heart abnormalities.

Conclusions: ACC may occur alone or be related to other abnormal clinical phenotypes, and its genetic mechanism is very complicated. These results revealed ACC is associated with a variety of chromosomal abnormalities. The findings of the present study expand the genotypes associated with ACC, and further delineation of the genotype–phenotype correlations for ACC. With current applications of chromosome microarray analysis, congenital submicroscopic copy-number variations in fetuses can be detected more effectively.

Article available in PDF format

View PDF Download PDF file

References

  1. Dupont C, Castellanos-Ryan N, Séguin JR, et al. The predictive value of head circumference growth during the first year of life on early child traits. Sci Rep. 2018; 8(1): 9828.
  2. Paul LK, Brown WS, Adolphs R, et al. Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity. Nat Rev Neurosci. 2007; 8(4): 287–299.
  3. Edwards TJ, Sherr EH, Barkovich AJ, et al. Clinical, genetic and imaging findings identify new causes for corpus callosum development syndromes. Brain. 2014; 137(Pt 6): 1579–1613.
  4. Margari L, Palumbi R, Campa MG, et al. Clinical manifestations in children and adolescents with corpus callosum abnormalities. J Neurol. 2016; 263(10): 1939–1945.
  5. Yao G, Chen XN, Flores-Sarnat L, et al. Deletion of chromosome 21 disturbs human brain morphogenesis. Genet Med. 2006; 8(1): 1–7.
  6. Graham JM, Superneau D, Rogers RC, et al. Clinical and behavioral characteristics in FG syndrome. Am J Med Genet. 1999; 85(5): 470–475.
  7. Revanna KG, Rajadurai VS, Chandran S. Agenesis of the corpus callosum with interhemispheric cyst: clinical implications and outcome. BMJ Case Rep. 2018; 11(1).
  8. Weiss K, Wigby K, Fannemel M, et al. Haploinsufficiency of ZNF462 is associated with craniofacial anomalies, corpus callosum dysgenesis, ptosis, and developmental delay. Eur J Hum Genet. 2017; 25(8): 946–951.
  9. Guen VJ, Edvardson S, Fraenkel ND, et al. A homozygous deleterious CDK10 mutation in a patient with agenesis of corpus callosum, retinopathy, and deafness. Am J Med Genet A. 2018; 176(1): 92–98.
  10. Tripathy R, Leca I, van Dijk T, et al. Mutations in MAST1 cause mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations. Neuron. 2018; 100(6): 1354–1368.e5.
  11. O'Driscoll MC, Black GCM, Clayton-Smith J, et al. Identification of genomic loci contributing to agenesis of the corpus callosum. Am J Med Genet A. 2010; 152A(9): 2145–2159.
  12. Palmer EE, Mowat D. Agenesis of the corpus callosum: a clinical approach to diagnosis. Am J Med Genet C Semin Med Genet. 2014; 166C(2): 184–197.
  13. Romaniello R, Marelli S, Giorda R, et al. Clinical characterization, genetics, and long-term follow-up of a large cohort of patients with agenesis of the corpus callosum. J Child Neurol. 2017; 32(1): 60–71.
  14. Stevens-Kroef M, Simons A, Rack K, et al. Cytogenetic Nomenclature and Reporting. Methods Mol Biol. 2017; 1541: 303–309.
  15. Wan S, Zheng Y, Dang Y, et al. Prenatal diagnosis of 17q12 microdeletion and microduplication syndrome in fetuses with congenital renal abnormalities. Mol Cytogenet. 2019; 12: 19.
  16. Song T, Wan S, Li Yu, et al. Detection of copy number variants using chromosomal microarray analysis for the prenatal diagnosis of congenital heart defects with normal karyotype. J Clin Lab Anal. 2019; 33(1): e22630.
  17. She Q, Fu F, Guo X, et al. Genetic testing in fetuses with isolated agenesis of the corpus callosum. J Matern Fetal Neonatal Med. 2021; 34(14): 2227–2234.
  18. Marsh APL, Heron D, Edwards TJ, et al. Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance. Nat Genet. 2017; 49(4): 511–514.
  19. Luckie TM, Potter SL, Bacino CA, et al. Agenesis of the corpus callosum and hepatoblastoma. Am J Med Genet A. 2020; 182(1): 224–228.
  20. Bartha-Doering L, Schwartz E, Kollndorfer K, et al. Effect of corpus callosum agenesis on the language network in children and adolescents. Brain Struct Funct. 2021; 226(3): 701–713.
  21. Zhan D, Li H, Shi W, et al. Social-emotional, sleep and feeding problems in young patients with agenesis of the corpus callosum and the life quality of their parents. Soc Neurosci. 2021; 16(2): 166–173.
  22. Callaway JLA, Shaffer LG, Chitty LS, et al. The clinical utility of microarray technologies applied to prenatal cytogenetics in the presence of a normal conventional karyotype: a review of the literature. Prenat Diagn. 2013; 33(12): 1119–1123.
  23. Chang Q, Yang Y, Peng Y, et al. Prenatal detection of chromosomal abnormalities and copy number variants in fetuses with ventriculomegaly. Eur J Paediatr Neurol. 2020; 25: 106–112.
  24. Barber JCK, Rosenfeld JA, Foulds N, et al. 8p23.1 duplication syndrome; common, confirmed, and novel features in six further patients. Am J Med Genet A. 2013; 161A(3): 487–500.
  25. Al Shehhi M, Forman EB, Fitzgerald JE, et al. NRXN1 deletion syndrome; phenotypic and penetrance data from 34 families. Eur J Med Genet. 2019; 62(3): 204–209.
  26. Lloveras E, Canellas A, Barranco L, et al. A new case with corpus callosum abnormalities, microcephaly and seizures associated with a 2.3-mb 1q43-q44 deletion. Cytogenet Genome Res. 2019; 159(3): 126–129.
  27. Peddibhotla S, Nagamani SCS, Erez A, et al. Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27. Eur J Hum Genet. 2015; 23(1): 54–60.
  28. Boland E, Clayton-Smith J, Woo VG, et al. Mapping of deletion and translocation breakpoints in 1q44 implicates the serine/threonine kinase AKT3 in postnatal microcephaly and agenesis of the corpus callosum. Am J Hum Genet. 2007; 81(2): 292–303.
  29. Chen CP, Ko TM, Wang LK, et al. Prenatal diagnosis and molecular cytogenetic characterization of a chromosome 1q42.3-q44 deletion in a fetus associated with ventriculomegaly on prenatal ultrasound. Taiwan J Obstet Gynecol. 2020; 59(4): 598–603.
  30. Bedeschi MF, Bonaglia MC, Grasso R, et al. Agenesis of the corpus callosum: clinical and genetic study in 63 young patients. Pediatr Neurol. 2006; 34(3): 186–193.
  31. Rubtsov N, Senger G, Kuzcera H, et al. Interstitial deletion of chromosome 6q: precise definition of the breakpoints by microdissection, DNA amplification, and reverse painting. Hum Genet. 1996; 97(6): 705–709.
  32. Shen-Schwarz S, Hill LM, Surti U, et al. Deletion of terminal portion of 6q: report of a case with unusual malformations. Am J Med Genet. 1989; 32(1): 81–86.
  33. Sukumar S, Wang S, Hoang K, et al. Subtle overlapping deletions in the terminal region of chromosome 6q24.2-q26: three cases studied using FISH. Am J Med Genet. 1999; 87(1): 17–22.
  34. Yamanouchi H, Imataka G, Nakagawa E, et al. An analysis of epilepsy with chromosomal abnormalities. Brain Dev. 2005; 27(5): 370–377.
  35. Bhatia MS, Saha R, Doval N. Delusional disorder in a patient with corpus callosum agenesis. J Clin Diagn Res. 2016; 10(12): VD01–VD02.