Congenital Hydrocephalus and Hemivertebrae Associated With De NOVO Partial Monosomy 6q (6q25.3→qter)

Li, Y; Choy, K-W; Xie, H-N; Chen, M; He, W-Y; Gong, Y-F; Liu, H-Y; Song, Y-Q; Xian, Y-X; Sun, X-F; Chen, Xin-Jie

doi:10.1515/bjmg-2015-0009

Abstract

This study was conducted to describe a prenatal case of congenital hydrocephalus and hemivertebrae with a 6q terminal deletion and to investigate the possible correlation between the genotype and phenotype of the proband. We performed an array-based comparative genomic hybridization (aCGH) analysis on a fetus diagnosed with congenital hydrocephalus and hemivertebrae. The deletion, spanning 10.06 Mb from 6q25.3 to 6qter, was detected in this fetus. The results of aCGH, karyotype and fluorescent in situ hybridization (FISH) analyses in the healthy parents were normal, which confirmed that the proband’s copy- number variant (CNV) was de novo. This deleted region encompassed 97 genes, including 28 OMIM genes. We discussed four genes (TBP, PSMB1, QKI and Pacrg) that may be responsible for hydrocephalus while the T gene may have a role in hemivertebra. We speculate that five genes in the 6q terminal deletion region were potentially associated with hemivertebrae and hydrocephalus in the proband.

References

1. Elia M, Striano P, Fichera M, Gaggero R, Castiglia L, Galesi O, et al. 6q Terminal deletion syndrome associated with a distinctive EEG and clinical pattern: A report of five cases. Epilepsia. 2006; 47(5): 830-838.10.1111/j.1528-1167.2006.00522.x16686647
Search in Google Scholar
2. Eash D, Waggoner D, Chung J, Stevenson D, Martin CL. Calibration of 6q subtelomere deletions to define genotype/phenotype correlations. Clin Genet. 2005; 67(5): 396-403.10.1111/j.1399-0004.2005.00424.x15811006
Search in Google Scholar
3. Lee JY, Cho YH, Hallford G. Delineation of subtelomeric deletion of the long arm of chromosome 6. Ann Hum Genet. 2011; 75(6): 755-764.10.1111/j.1469-1809.2011.00675.x21950800
Search in Google Scholar
4. Michelson M, Ben-Sasson A, Vinkler C, Leshinsky- Silver E, Netzer I, Frumkin A, et al. Delineation of the interstitial 6q25 microdeletion syndrome: Refinement of the critical causative region. Am J Med Genet A. 2012; 158A(6): 1395-1399.10.1002/ajmg.a.3536122585544
Search in Google Scholar
5. Wadt K, Jensen LN, Bjerglund L, Lundstrom M, Kirchhoff M, Kjaergaard S. Fetal ventriculomegaly due to familial submicroscopic terminal 6q deletions. Prenat Diagn. 2012; 32(12): 1212-1217.10.1002/pd.398123065819
Search in Google Scholar
6. McMaster MJ, David CV. Hemivertebra as a cause of scoliosis. A study of 104 patients. J Bone Joint Surg Br. 1986; 68(4): 588-595
Search in Google Scholar
7. Goldstein I, Makhoul IR, Weissman A, Drugan A. Hemivertebra: Prenatal diagnosis, incidence and characteristics. Fetal Diagn Ther. 2005; 20(2): 121-126.10.1159/00008243515692206
Search in Google Scholar
8. Connor JM, Conner AN, Connor RA, Tolmie JL, Yeung B, Goudie D. Genetic aspects of early childhood scoliosis. Am J Med Genet. 1987; 27(2): 419-424.10.1002/ajmg.13202702203300334
Search in Google Scholar
9. Leung YL, Buxton N. Combined diastematomyelia and hemivertebra: A review of the management at a single centre. J Bone Joint Surg Br. 2005; 87(10): 1380-1384.
Search in Google Scholar
10. Chen M, Chan B, Lam TP, Shek T, Lee CP, Tang MH. Sonographic features of hemivertebra at 13 weeks’ gestation. J Obstet Gynaecol Res. 2007; 33(1): 74-77.10.1111/j.1447-0756.2007.00483.x17212670
Search in Google Scholar
11. Leung TY, Vogel I, Lau TK, Chong W, Hyett JA, Petersen OB, et al. Identification of submicroscopic chromosomal aberrations in fetuses with increased nuchal translucency and apparently normal karyotype. Ultrasound Obstet Gynecol. 2011; 38(3): 314-319.10.1002/uog.898821400624
Search in Google Scholar
12. Wax JR, Watson WJ, Miller RC, Ingardia CJ, Pinette MG, Cartin A, et al. Prenatal sonographic diagno-sis of hemivertebrae: Associations and outcomes. J Ultrasound Med. 2008; 27(7): 1023-1027.10.7863/jum.2008.27.7.102318577665
Search in Google Scholar
13. Imaizumi K, Masuno M, Ishii T, Kuroki Y, Okuzumi N, Nakamura Y. Congenital scoliosis (hemi vertebra) associated with de novo balanced reciprocal translocation, 46,XX,t(13;17)(q34;p11.2). Am J Med Genet. 1997; 73(3): 244-246.10.1002/(SICI)1096-8628(19971219)73:3<244::AID-AJMG2>3.0.CO;2-S
Search in Google Scholar
14. Ghebranious N, Blank RD, Raggio CL, Staubli J, McPherson E, Ivacic L, et al. A missense T (Brachyury) mutation contributes to vertebral malformations. J Bone Miner Res. 2008; 23(10): 1576-1583.10.1359/jbmr.080503
Search in Google Scholar
15. Verhagen JM, Schrander-Stumpel CT, Krapels IP, de Die-Smulders CE, van Lint FH, Willekes C, et al. Congenital hydrocephalus in clinical practice: A genetic diagnostic approach. Eur J Med Genet. 2011; 54(6): e542-e547.10.1016/j.ejmg.2011.06.005
Search in Google Scholar
16. Davis GH. Fetal hydrocephalus. Clin Perinatol. 2003; 30(3): 531-539.10.1016/S0095-5108(03)00053-8
Search in Google Scholar
17. Garne E, Loane M, Addor MC, Boyd PA, Barisic I, Dolk H. Congenital hydrocephalus ‒ prevalence, prenatal diagnosis and outcome of pregnancy in four European regions. Eur J Paediatr Neurol. 2010; 14(2): 150-155.10.1016/j.ejpn.2009.03.005
Search in Google Scholar
18. Li P, Pomianowski P, DiMaio MS, Florio JR, Rossi MR, Xiang B, et al. Genomic characterization of prenatally detected chromosomal structural abnormalities using oligonucleotide array comparative genomic hybridization. Am J Med Genet A. 2011; 155A(7): 1605-1615.10.1002/ajmg.a.34043
Search in Google Scholar
19. Rooms L, Reyniers E, Scheers S, van Luijk R, Wauters J, Van Aerschot L, et al. TBP as a candidate gene for mental retardation in patients with subtelomeric 6q deletions. Eur J Hum Genet. 2006; 14(10): 1090-1096.10.1038/sj.ejhg.5201674
Search in Google Scholar
20. Abu-Amero KK, Hellani A, Salih MA, Al Hussain A, al Obailan M, Zidan G, et al. Ophthalmologic abnormalities in a de novo terminal 6q deletion. Ophthalmic Genet. 2010; 31(1): 1-11.10.3109/13816810903312535
Search in Google Scholar
21. Backx L, Fryns JP, Marcelis C, Devriendt K, Vermeesch J, Van Esch H. Haploinsufficiency of the gene Quaking (QKI) is associated with the 6q terminal deletion syndrome. Am J Med Genet A. 2010; 152A(2): 319-326.10.1002/ajmg.a.33202
Search in Google Scholar
22. Aberg K, Saetre P, Jareborg N, Jazin E. Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia. Proc Natl Acad Sci USA. 2006; 103(19): 7482-7487.10.1073/pnas.0601213103
Search in Google Scholar
23. Wilson GR, Wang HX, Egan GF, Robinson PJ, Delatycki MB, O’Bryan MK, et al. Deletion of the Parkin co-regulated gene causes defects in ependymal ciliary motility and hydrocephalus in the quakingviable mutant mouse. Hum Mol Genet. 2010; 19(8): 1593-1602.10.1093/hmg/ddq03120106870
Search in Google Scholar
24. Peddibhotla S, Nagamani SC, Erez A, Hunter JV, Holder JL Jr, Carlin ME, 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): 54-60.10.1038/ejhg.2014.51426673724736736
Search in Google Scholar
25. Bettenhausen B, Hrabe de Angelis M, Simon D, Guenet JL, Gossler A. Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta. Development (Cambridge, UK). 1995; 121(8): 2407-2418. 10.1242/dev.121.8.24077671806
Search in Google Scholar

Congenital Hydrocephalus and Hemivertebrae Associated With De NOVO Partial Monosomy 6q (6q25.3→qter)

Abstract

Paradigm

My account