Chromosomal abnormalities that result in genomic imbalances are a major cause of congenital and developmental anomalies. Partial duplication of chromosome 3q syndrome is a well-described condition, and the phenotypic manifestations include a characteristic facies, microcephaly, hirsutism, synophrys, broad nasal bridge, congenital heart disease, genitourinary disorders, and mental retardation. Approximately 60%–75% of cases are derived from a balanced translocation. We describe a family with a pure typical partial trisomy 3q syndrome derived from a maternal balanced translocation t(3;13)(q26.2;p11.2). As the chromosomal rearrangement involves the short arm of an acrocentric chromosome, the phenotype corresponds to a pure trisomy 3q26.2-qter syndrome. There are 4 affected individuals and several carriers among three generations. The report of this family is relevant because there are few cases of pure duplication 3q syndrome reported, and the cases described here contribute to define the phenotype associated with the syndrome. Furthermore, we confirmed that the survival until adulthood is possible. This report also identified the presence of glycosaminoglycans in urine in this family, not related to the chromosomal abnormality or the phenotype. 1. Introduction Chromosomal abnormalities that result in genomic imbalances are a major cause of congenital and developmental anomalies including multiple congenital malformations and mental retardation [1]. They can result from a numerical imbalance or from a structural change in the chromosomes resulting in partial deletions and/or duplications. Partial duplication of chromosome 3q syndrome (dup(3q)) is a well-described condition that has overlapping features with the Brachmann de Lange syndrome (MIM 122470) [2–4]. The phenotypic manifestations include a characteristic facies, microcephaly, hirsutism, synophrys, broad nasal bridge, congenital heart disease, genitourinary disorders, and mental retardation [5]. In approximately 60%–75% of cases, it is derived from a balanced translocation [2, 6, 7], which also presents a concomitant deletion of another chromosome; however, the clinical manifestations appear to be dominated by the dup(3q) phenotype [3, 8]. Some of the reported cases are pure partial trisomies that allowed to define a critical region in 3p26.3-q27 [2, 5, 9–11]. Here we report the clinical, cytogenetic, and biochemical characteristics of 4 patients belonging to the same family with an inherited pure duplication of 3q26.2-qter resulting from an adjacent 1 segregation from a balanced maternal
References
[1]
D. H. Park, S. Lim, E. S. Park, et al., “A nine-month-old boy with isodicentric chromosome 15: a case report,” Annals of Rehabilitation Medicine, vol. 37, no. 2, pp. 291–294, 2013.
[2]
A. J. van Essen, K. Kok, A. van den Berg et al., “Partial 3q duplication syndrome and assignment of D3S5 to 3q25-3q28,” Human Genetics, vol. 87, no. 2, pp. 151–154, 1991.
[3]
M. S. Aqua, P. Rizzu, E. A. Lindsay et al., “Duplication 3q syndrome: molecular delineation of the critical region,” American Journal of Medical Genetics, vol. 55, no. 1, pp. 33–37, 1995.
[4]
A. L. Shanske, J. Leonard, O. Nahum, D. L. Coppock, and B. Levy, “Delineation of the breakpoints of pure duplication 3q due to a de novo duplication event using SOMA,” American Journal of Medical Genetics A, vol. 152, no. 12, pp. 3185–3188, 2010.
[5]
B. H. W. Faas, B. B. A. de Vries, J. van Es-van Gaal, G. Merkx, J. M. T. Draaisma, and D. F. C. M. Smeets, “A new case of dup(3q) syndrome due to a pure duplication of 3qter,” Clinical Genetics, vol. 62, no. 4, pp. 315–320, 2002.
[6]
L. J. Sciorra, K. Bahng, and M. I. Lee, “Trisomy in the distal end of the long arm of chromosome 3: a condition clinically similar to the Cornelia de Lange syndrome,” American Journal of Diseases of Children, vol. 133, no. 7, pp. 727–730, 1979.
[7]
P. Steinbach, W. N. Adkins Jr., and H. Caspar, “The dup(3q) syndrome: report of eight cases and review of the literature,” American Journal of Medical Genetics, vol. 10, no. 2, pp. 159–177, 1981.
[8]
M. Meins, J. K. Hagh, F. Gerresheim et al., “Novel case of dup(3q) syndrome due to a de novo interstitial duplication 3q24-q26.31 with minimal overlap to the dup(3q) critical region,” American Journal of Medical Genetics, vol. 132, no. 1, pp. 84–89, 2005.
[9]
G. N. Wilson, V. C. Hieber, and R. D. Schmickel, “The association of chromosome 3 duplication and the Cornelia de Lange syndrome,” Journal of Pediatrics, vol. 93, no. 5, pp. 783–788, 1978.
[10]
W. Rosenfeld, R. S. Verma, R. C. Jhaveri, R. Estrada, H. Evans, and H. Dosik, “Duplication 3q: severe manifestations in an infant with duplication of a short segment of 3q,” American Journal of Medical Genetics, vol. 10, no. 2, pp. 187–192, 1981.
[11]
V. Grossmann, D. Müller, W. Müller et al., “‘Essentially’ pure trisomy 3q27 → qter: further delineation of the partial trisomy 3q phenotype,” American Journal of Medical Genetics A, vol. 149, no. 11, pp. 2522–2526, 2009.
[12]
M. P. Gallegos-Arreola, M. V. Machorro-Lazo, S. E. Flores-Martínez et al., “Urinary glycosaminoglycan excretion in healthy subjects and in patients with mucopolysaccharidoses,” Archives of Medical Research, vol. 31, no. 5, pp. 505–510, 2000.
[13]
S. Nampoothiri, K. Mahesh, K. R. Hiran, and V. Sunitha, “Sly disease: mucopolysaccharidosis type VII,” Indian Pediatrics, vol. 45, no. 10, pp. 859–861, 2008.
[14]
S. Tomatsu, A. M. Montano, V. C. Dung, J. H. Grubb, and W. S. Sly, “Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (sly syndrome),” Human Mutation, vol. 30, no. 4, pp. 511–519, 2009.
[15]
R. Vervoort, M. R. Islam, W. Sly et al., “A pseudodeficiency allele (D152N) of the human β-glucuronidase gene,” American Journal of Human Genetics, vol. 57, no. 4, pp. 798–804, 1995.
[16]
A. Pires, L. Ramos, M. Venancio, A. I. Rei, S. Castedo, and J. Saraiva, “Prenatal foetal diagnosis of partial trisomy 3q and monosomy 13p due to a maternal balanced rearrangement,” Prenatal Diagnosis, vol. 25, no. 4, pp. 292–295, 2005.
[17]
A. Falek, R. Schmidt, and G. A. Jervis, “Familial de Lange syndrome with chromosome abnormalities,” Pediatrics, vol. 37, no. 1, pp. 92–101, 1966.
[18]
S. H. Jung, S. H. Shim, S. H. Park et al., “Prenatal diagnosis of partial trisomy 3q resulting from t(3;14) in a fetus with multiple anomalies including vermian hypoplasia,” Gene, vol. 498, no. 2, pp. 237–241, 2012.
[19]
P. Rizzu and A. Baldini, “Subchromosomal band interval mapping and ordering of DNA markers in the region 3q26.3-q27 involved in the dup(3q) syndrome,” Genomics, vol. 24, no. 3, pp. 580–582, 1994.
[20]
H. Zhu, Y. Hu, R. Zhu, Y. Yang, X. Zhu, and W. Wang, “A boy with partial trisomy of chromosome 3q24-q28 from paternal balanced insertion and multiple congenital anomalies,” American Journal of Medical Genetics A, vol. 161, no. 2, pp. 327–330, 2013.
[21]
B. C. Ballif, A. Theisen, J. Coppinger, et al., “Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication,” Molecular Cytogenetics, vol. 1, article 8, 2008.
[22]
S. Goobie, J. Knijnenburg, D. FitzPatrick et al., “Molecular and clinical characterization of de novo and familial cases with microduplication 3q29: guidelines for copy number variation case reporting,” Cytogenetic and Genome Research, vol. 123, no. 1–4, pp. 65–78, 2009.
[23]
E. C. Lisi, A. Hamosh, K. F. Doheny et al., “3q29 interstitial microduplication: a new syndrome in a three-generation family,” American Journal of Medical Genetics A, vol. 146, no. 5, pp. 601–609, 2008.
[24]
O. Cohen, M.-A. Mermet, and J. Demongeot, “HC forum: a web site based on an international human cytogenetic database,” Nucleic Acids Research, vol. 29, no. 1, pp. 305–307, 2001.
F. Aleixander Blanquer, I. Manchón Trives, M. J. Forniés Arnau, et al., “Síndrome de microduplicación 3q29,” Anales de Pediatría, vol. 75, no. 6, pp. 409–412, 2011.
