Congenital heart defect (CHD) is the most common form of birth defects. There is a high association between increased nuchal translucency and CHD in fetuses, and CHD in the antenatal period has a high incidence of 22q11.2 deletion syndrome (22q11.2DS). Apart from 22q11.2DS, the BRUNOL3 gene at 10p14 is also associated with DiGeorge-like features. We studied a total of 110 pre- and postnatal CHD cases with FISH probes. 22q11.2DS was detected in 5 cases and 10p14 deletion in 1 case. Antenatally diagnosed cases of CHD should be investigated by karyotyping and 22q11.2DS testing. Cases with increased nuchal translucency, intrauterine growth retardation, and other non-cardiac malformations because of 22q11.2DS should be screened carefully for thymus dysgenesis. It is also advisable to screen patients referred for 22q11.2DS for a 10p14 deletion, therefore enabling appropriate parental counseling.

Keywords:
10p14, 22q11.2 deletion syndrome, Congenital heart defect
1.
Bartsch O, Nemecková M, Kocárek E, Wagner A, Puchmajerová A, et al: DiGeorge/velocardiofacial syndrome: FISH studies of chromosomes 22q11 and 10p14, and clinical reports on the proximal 22q11 deletion. Am J Med Genet 117A:1-5 (2003).
2.
Behrman RE, Kliegman RM, Jenson HB: Congenital heart disease, in RE Behrman, RM Kliegman, HB Jenson (eds): Nelson Textbook of Pediatrics, ed 16, pp 1362-1363 (Harcourt Asia Pvt. Ltd, Philadelphia 2000).
3.
Berend SA, Spikes AS, Kashork CD, Wu JM, Daw SC, et al: Dual-probe fluorescence in situ hybridization assay for detecting deletions associated with VCFS/DiGeorge syndrome I and DiGeorge syndrome II loci. Am J Med Genet 91:313-317 (2000).
4.
Besseau-Ayasse J, Violle-Poirsier C, Bazin A, Gruchy N, Moncla A, et al: A French collaborative survey of 272 fetuses with 22q11.2 deletion: ultrasound findings, fetal autopsies and pregnancy outcomes. Prenat Diagn 34:424-430 (2014).
5.
Boudjemline Y, Fermont L, Le Bidois J, Villain E, Sidi D, et al: Can we predict 22q11 status of fetuses with tetralogy of Fallot? Prenat Diagn 22:231-234 (2002).
6.
Bretelle F, Beyer L, Pellissier MC, Missirian C, Sigaudy S, et al: Prenatal and postnatal diagnosis of 22q11.2 deletion syndrome. Eur J Med Genet 53:367-370 (2010).
7.
Burnside RD: 22q11.21 deletion syndromes: a review of proximal, central, and distal deletions and their associated features. Cytogenet Genome Res 146:89-99 (2015).
8.
Chen M, Yang YS, Shih JC, Lin WH, Lee DJ, et al: Microdeletions/duplications involving TBX1 gene in fetuses with conotruncal heart defects which are negative for 22q11.2 deletion on fluorescence in-situ hybridization. Ultrasound Obstet Gynecol 43:396-403 (2014).
9.
Elliott D, Thomas GH, Condron CJ, Khuri N, Richardson F: C-group chromosome abnormality (?10p-). Am J Dis Child 119:72-73 (1970).
10.
Fukai R, Ochi N, Murakami A, Nakashima M, Tsurusaki Y, et al: Co-occurrence of 22q11 deletion syndrome and HDR syndrome. Am J Med Genet A 161A:2576-2581 (2013).
11.
Gao W, Higaki T, Eguchi-Ishimae M, Iwabuki H, Wu Z, et al: DGCR6 at the proximal part of the DiGeorge critical region is involved in conotruncal heart defects. Human Genome Variation DOI: 10.1038/hgv.2015.4 (2015).
12.
Gawde H, Patel ZM, Khatkhatey MI, D'Souza A, Babu S, et al: Chromosome 22 microdeletion by F.I.S.H. in isolated congenital heart disease. Indian J Pediatr 73:885-888 (2006).
13.
Halford S, Wilson DI, Daw SC, Roberts C, Wadey R, et al: Isolation of a gene expressed during early embryogenesis from the region of 22q11 commonly deleted in DiGeorge syndrome. Hum Mol Genet 2:1577-1582 (1993).
14.
Hervé J, Warnet JF, Jeaneau-Bellego E, Portnoi MF, Taillemitte JL, Hervé F: Partial monosomy of the short arm of chromosome 10, associated with Rieger's syndrome and a Di George type partial immunodeficiency. Ann Pediatr (Paris) 31:77-80 (1984).
15.
Hungerford DA: Leukocytes cultured from small inocula of whole blood and the preparation of metaphase chromosomes by treatment with hypotonic KCl. Stain Technol 40:333-338 (1965).
16.
Iserin L, de Lonlay P, Viot G, Sidi D, Kachaner J, et al: Prevalence of the microdeletion 22q11 in newborn infants with congenital conotruncal cardiac anomalies. Eur J Pediatr 157:881-884 (1998).
17.
Kobrynski LJ, Sullivan KE: Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 370:1443-1452 (2007).
18.
Lamouroux A, Mousty E, Prodhomme O, Bigi N, Le Gac MP, et al: Absent or hypoplastic thymus: a marker for 22q11.2 microdeletion syndrome in case of polyhydramnios. J Gynecol Obstet Biol Reprod (Paris) 45:388-396 (2016).
19.
Levy-Mozziconacci A, Piquet C, Heurtevin PC, Philip N: Prenatal diagnosis of 22q11 microdeletion. Prenatal Diagn 17:1033-1037 (1997).
20.
Lichtner P, Konig R, Hasegawa T, Van Esch H, Meitinger T, et al: An HDR (hypoparathyroidism, deafness, renal dysplasia) syndrome locus maps distal to the DiGeorge syndrome region on 10p13/14. J Med Genet 37:33-37 (2000).
21.
Lichtner P, Attié-Bitach T, Schuffenhauer S, Henwood J, Bouvagnet P, et al: Expression and mutation analysis of BRUNOL3, a candidate gene for heart and thymus developmental defects associated with partial monosomy 10p. J Mol Med 80:431-442 (2002).
22.
Liu T, Liu Q, Wang YX, Yang D, Xin Y, et al: Use of amniocytes for prenatal diagnosis of 22q11.2 microdeletion syndrome: a feasibility study. Chin Med J 123:438-442 (2010).
23.
Madon PF, Athalye AS, Sanghavi K, Parikh FR: Microdeletion syndromes detected by FISH -73 positive from 374 cases. Int J Hum Genet 10:15-20 (2010).
24.
McDonald-McGinn DM, Zackai EH: Genetic counseling for the 22q11.2.Dev. Disabil Res Rev 14:69-74 (2008).
25.
Payne M, Johnson MC, Grant JW, Strauss AW: Towards a molecular understanding of congenital heart disease. Circulation 91:494-504 (1995).
26.
Pinkel D, Landegent J, Collins C, Fuscoe J, Segraves R, et al: Fluorescence in situ hybridization with human chromosome-specific libraries: detection of trisomy 21 and translocations of chromosome 4. Proc Natl Acad Sci USA 85:9138-9142 (1988).
27.
Pretto D, Maar D, Yrigollen CM, Regan J, Tassone F: Screening newborn blood spots for 22q11.2 deletion syndrome using multiplex droplet digital PCR. Clin Chem 61:182-190 (2015).
28.
Priest JH, Rao KW: Prenatal chromosome diagnosis, in Barch MJ, Knutsen T, Spurbeckeds JL (eds): The AGT Cytogenetics Laboratory Manual, ed 3, pp 199-258 (Lippincott-Raven Publishers, Philadelphia 1997).
29.
Ried T, Baldini AR, Rand TC, Ward DC: Simultaneous visualization of seven different DNA probes by in situ hybridization using combinatorial fluorescence and digital imaging microscopy. Proc Natl Acad Sci USA 89:1388-1392 (1992).
30.
Sambrook J, Russell DW: Working with bacterial artificial chromosomes; in Sambrook J, Russell DW (eds): Molecular Cloning: A Laboratory Manual, ed 3, p 4.48 (CSHL Press, New York 2001).
31.
Schuffenhauer S, Seidel H, Oechsler H, Belohradsky B, Bernsau U, et al: DiGeorge syndrome and partial monosomy 10p: case report and review. Ann Genet 38:162-67 (1995).
32.
Schuffenhauer S, Lichtner P, Peykar-Derakhshandeh P, Murken J, Haas OA, et al: Deletion mapping on chromosome 10p and definition of a critical region for the second DiGeorge syndrome locus (DGS2). Europ J Hum Genet 6:213-225 (1998).
33.
Seabright M: A rapid banding technique for human chromosomes. Lancet 2:971-972 (1971).
34.
Shaffer LG, McGowan-Jordan J, Schmid M (eds): An International System for Human Cytogenetic Nomenclature (S. Karger, Basel 2013).
35.
Shapira M, Borochowitz A, Bar-El H, Dar H, Etzioni A, et al: Deletion of the short arm of chromosome 10 (10p13): report of a patient and review. Am J Med Genet 52:34-38 (1994).
36.
Shprintzen RJ: Velo-cardio-facial syndrome: 30 years of study. Dev Disabil Res Rev 14:3-10 (2008).
37.
Smitha R, Karat SC, Narayanappa D, Krishnamurthy B, Prasanth SN, et al: Prevalence of congenital heart diseases in Mysore. Indian J Hum Genet 12:11-16 (2006).
38.
Snijders R, Nicolaides K: First trimester diagnosis of chromosomal defects, in Nicolaides K (ed): The 11-13+6 Weeks Scan, pp 7-44 (Fetal Medicine Foundation, London 2004)
39.
Tank S, Malik S, Joshi S: Epidemiology of congenital heart disease among hospitalised patients. Bombay Hospital J 46:10 (2004).
40.
van Esch H, Groenen P, Fryns JP, Van de Ven W, Devriendt K: The phenotypic spectrum of the 10p deletion syndrome versus the classical DiGeorge syndrome. Genet Couns 10:59-65 (1999).
41.
Van L, Butcher NJ, Costain G, Ogura L, Chow EW, et al: Fetal growth and gestational factors as predictors of schizophrenia in 22q11.2 deletion syndrome. Genet Med 18:350-355 (2016).
42.
Volpe P, Marasini M, Caruso G, Marzullo A, Buonadonna AL, et al: 22q11 deletions in fetuses with malformations of the outflow tracts or interruption of the aortic arch: impact of additional ultrasound signs. Prenat Diagn 23:752-757 (2003).
43.
Yatsenko SA, Yatsenko AN, Szigeti K, Craigen WJ, Stankiewicz P, et al: Interstitial deletion of 10p and atrial septal defect in DiGeorge 2 syndrome. Clin Genet 66:128-136 (2004).
44.
Yatsenko SA, Peters DG, Saller DN, Chu T, Clemens M, et al: Maternal cell-free DNA-based screening for fetal microdeletion and the importance of careful diagnostic follow-up. Genet Med 17:836-838 (2015).
45.
Yagi H, Furutani Y, Hamada H, Sasaki T, Asakawa S, et al: Role of TBX1 in human del22q11.2 syndrome. Lancet 362:1366-1373 (2003).
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