Interstitial Deletion 4q due to a Complex Rearrangement Involving Chromosomes 1, 2, 4, 8, 14 and 16
Abstract
Complex chromosome rearrangements (CCR’s) involving multiple breaks in two or more chromosomes are rare. The precise characterization of a CCR is difficult and may be inaccurate even by using molecular cytogenetic techniques. Various new molecular techniques such as MLPA, array techniques (CGH, BAC, oligo, SNP, etc.) have proved to be powerful tools for the characterization of CCR’s. We present here a patient with a de novo CCR involving chromosomes 1, 2, 4, 8, 14, 16. He was investigated cytogenetically because of multiple congenital anomalies such as macrocephaly with a prominent forehead, epicanthus, ptosis, micrognathia, low set ears, short neck, pectus excavatum, adducted right foot, cryptorchidism, hypotonia and neurodevelopmental delay. Cytogenetic analysis revealed an abnormal karyotype (46,XY,der(1),der(2),der(4),t(8;14),der(16)), while the parents had a normal chromosome count. After FISH investigations using different commercially available probes the karyotype was interpreted as ish t(1:16),ins(4;2),t(8;14). The rearrangements were apparently balanced at a 500-550 band level and revealed no obvious explanation for the phenotype of the index patient. Therefore, an array-CGH analysis (NimbleGen) was initiated and a 14,7 Mb gross deletion was found in chromosome 4q(del(4)(q21.23q23)) including approximately 50 genes.References
Jacobs PA, Browne C, Gregson N, Joyce C, White H. Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding. J Med Genet 1992;29:103-8.
Kausch K, Haaf T, Köhler J, Schmid M. Complex chromosomal rearrangement in a woman with multiple miscarriages. Am J Med Genet 1988;31:415-20
Kousseff BG, Papenhausen P, Essig YP, Torres MP. Complex chromosome rearrangement with ankyloblepharon filiforme adnatum. J Med Genet 1993; 30:167-70.
Gribble SM, Prigmore E, Burford DC, Porter KM, Ng BL, Douglas EJ, Fiegler H, Carr P, Kalaitzopoulos D, Clegg S, Sandstrom R, Temple IK, Youings SA, Thomas NS, Dennis NR, Jacobs PA, Crolla JA, Carter NP. The complex nature of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes. J Med Genet 2005; 42:8-16.
Ballarati L, Recalcati MP, Bedeschi MF, Lalatta F, Valtorta C, Bellini M, Finelli P, Larizza L, Giardino D. Cytogenetic, FISH and array-CGH characterization of a complex chromosomal rearrangement carried by a mentally and language impaired patient. 2009; 52:218-23
Röthlisberger B, Kotzot D, Brecevic L, Koehler M, Balmer D, Binkert F, Schinzel A. Recombinant balanced and unbalanced translocations as a consequence of a balanced complex chromosomal rearrangement involving eight breakpoints in four chromosomes. Eur J Hum Genet 1999; 7:873-83.
Giardino D, Corti C, Ballarati L, Finelli P, Valtorta C, Botta G, Giudici M, Grosso E, Larizza L. Prenatal diagnosis of a de novo complex chromosome rearrangement (CCR) mediated by six breakpoints, and a review of 20 prenatally ascertained CCRs. Prenat Diagn 2006; 26:565-70.
Suwa K, Momoi MY, Yamagata T, Mori Y. Interstitial deletion of the long arm of chromosome 4 [del(4)(q21.22q23)] and a liver tumor.Am J Med Genet 1998; 78:291-3.
Te-Yao Hsu, Fu-Tsaı Kung, Chıa-Yu Ou, Pı-Yu Hsıao, Fu-Jen Huang, Chan-Chao Changchıen And Shıuh-Young Chang Prenatal Dıagnosıs Of De Novo interstitial deletıon of proxımal 4q by maternal serum screenıng for Down Syndrome Prenat Diagn 1998; 18: 1323–7
Nowaczyk M.J.M., I.E. Teshima, J. Siegel-Bartelt, J.T.R. Clarke. Deletion 4q21/4q22 Syndrome: Two Patients With De Novo 4q21.3q23 and 4q13.2q23 Deletions. American Journal of Medical Genetics 1997; 69:400–5
Hegmann KM, Spikes AS, Orr-Urtreger A, Shaffer LG. Segregation of a paternal insertional translocation results in partial 4q monosomy or 4q trisomy in two siblings. Am J Med Genet 1996; ;61:10-5.
Kulharya AS, Maberry M, Kukolich MK, Day DW, Schneider NR, Wilson GN, Tonk V Interstitial deletions 4q21.1q25 and 4q25q27: Phenotypic variability and relation to Rieger anomaly. Am J Med Genet 1995; 55:165–70.
Sijmons RH, Kristoffersson U, Tuerlings JHAM, Ljung R, Dijkhuis-Stoffelsma R, Breed ASPM. Piebaldism in a mentally retarded girl with rare deletion of the long arm of chromosome 4. Pediatr Dermatol 1993; 10:235–9.
Campbell JM, Williams J, Batcup G. Interstitial deletion of chromosome 4q diagnosed prenatally. J Med Genet 1986; 23:366–8.
Hoo JJ, Haslam RH, Van Oram C. Tentative assignment of piebald trait gene to chromosome band 4q12. Hum Genet 1986; 73:230–1.
Piovani G, Borsani G, Bertini V, Kalscheuer VM, Viertel P, Bellotti D, Valseriati D, Barlati S. Unexpected identification of two interstitial deletions in a patient with a pericentric inversion of a chromosome 4 and an abnormal phenotype. Eur J Med Genet 2006; 49:215-23.
Vieira, N. M., Naslavsky, M. S., Licinio, L., Kok, F., Schlesinger, D., Vainzof, M., Sanchez, N., Kitajima, J. P., Gal, L., Cavacana, N., Serafini, P. R., Chuartzman, S., Vasquez, C., Mimbacas, A., Nigro, V., Pavanello, R. C., Schuldiner, M., Kunkel, L. M., Zatz, M. A defect in the RNA-processing protein HNRPDL causes limb-girdle muscular dystrophy 1G (LGMD1G). Hum Molec Genet 2014: 23: 4103-10
Velinov M, Kupferman J, Gu H, Macera MJ, Babu A, Jenkins EC, Kupchik G. Polycystic kidneys and del (4)(q21.1q21.3): further delineation of a distinct phenotype Eur J Med Genet 2005;48:51-5.
Eggermann K, Bergmann C, Heil I, Eggermann T, Zerres K, Schüler HM. Rare proximal interstitial deletion of chromosome 4q, del(4)(q13.2q21.22): New case and comparison with the literature. Am J Med Genet A. 2005; 134A:226-8.
Beall MH, Falk RE, Ying KL. A patient with an interstitial deletion of the proximal portion of the long arm of chromosome 4. Am J Med Genet 1988; 31:553-7.
L.J. Butler, A.V. Palmer, T. Spencer, R. Tabios-Broadway, W.J. Wall. A new interstitial deletion of chromosome no. 4 del (4)(q22::q25), Clin Genet 1987; 31:199–205.
M.A. Curtis, O.W. Quarrell, A.M. Cobon, M. Cummins. Interstitial deletion of chromosome 4, del(4)(q12q21.1), in a child with multiple congenital abnormalities, J Med Genet 1990; 27:64–66.
N. Harada, T. Nagai, O. Shimokawa, N. Niikawa, N. Matsumotp, A 4q21-q22 deletion in a girl with severe growth retardation, Clin Genet 2002; 61: 226–8
