Volume 7, Issue 3, September 2019, Page: 50-54
Inherited Cryptic Translocation t(12;17)(q24.3;p13.3) Causing Recurrence of Miller-Dieker Syndrome
Elenice Ferreira Bastos, Clinical Cytogenetic Laboratory, Fernandes Figueira Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
Carlos Roberto da Fonseca, Clinical Cytogenetic Laboratory, Fernandes Figueira Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
Ingrid Bendas Feres Lima, Clinical Cytogenetic Laboratory, Fernandes Figueira Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
Maria de Jesus Esteves Camilo, Maternity School, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
Kleber da Silva Figueiredo, Biofisical Institute Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
Anna Luiza Vaz Serrão, Clinical Cytogenetic Laboratory, Fernandes Figueira Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
Sara Fabíola da Silva Oliveira, Clinical Cytogenetic Laboratory, Fernandes Figueira Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
Lucia de Fatima Marques de Moraes, Clinical Cytogenetic Laboratory, Fernandes Figueira Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
Juan Clinton Llerena Jr., Medical Genetic Department, Fernandes Figueira Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
Received: May 17, 2019;       Accepted: Jun. 26, 2019;       Published: Jul. 31, 2019
DOI: 10.11648/j.ijgg.20190703.12      View  98      Downloads  89
Abstract
The Miller-Dieker syndrome (MDS) is a severe neurological disorder characterized by lissencephaly, facial dysmorphies, global developmental delay and severe seizures. A deletion at 17p13.3, including the lissencephaly gene (LIS1), is usually present as part of a contiguous gene syndrome. Around 20% of case LSI1 gene is resulting from inherited balanced translocation. We present the case of a family with cryptic t(12;17) translocation identified by FISH in two generations. The proband had clinical features of MDS. The parents reported a paternal aunt deceased as a young infant due to “uncontrolled seizures and severe developmental delay. The GTG analysis of proband suggested deletion at 17p13.3 that was confirmed by FISH. The parental investigation by FISH revealed a paternal translocation involving regions 12qter and 17p13.3. This familial chromosomal rearrangement associated to MDS has modified the genetic counseling of the couple. From a very low risk of recurrence on the cases associated to a de novo del17p13.3, to a much higher risk, since it was associated to a familial translocation. This risk of recurrence, considering meiotic segregation of balanced translocation involving the 17p13.3 region is relatively high (12%) which alone would justify prenatal diagnosis. Classical and molecular cytogenetic investigations in the fetal sample were normal reassuring the couple as to a normal baby with neither 17p13.3 deletion nor carrier of the paternal translocation. This rare case identified by FISH demonstrate the need of providing molecular cytogenetic analysis for other family members; since, criptical balanced rearrangements may segregate undetected. This case evidences the importance of molecular study of parents of children with microdeletions, which could considerably improve the certainties regarding genetic counseling.
Keywords
Miller Dieker Syndrome, Cryptic Translocation, Microdeletion, Prenatal Diagnosis, Genetic Couseling
To cite this article
Elenice Ferreira Bastos, Carlos Roberto da Fonseca, Ingrid Bendas Feres Lima, Maria de Jesus Esteves Camilo, Kleber da Silva Figueiredo, Anna Luiza Vaz Serrão, Sara Fabíola da Silva Oliveira, Lucia de Fatima Marques de Moraes, Juan Clinton Llerena Jr., Inherited Cryptic Translocation t(12;17)(q24.3;p13.3) Causing Recurrence of Miller-Dieker Syndrome, International Journal of Genetics and Genomics. Vol. 7, No. 3, 2019, pp. 50-54. doi: 10.11648/j.ijgg.20190703.12
Copyright
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
Reiner O, Carrozzo R, Shen Y et al. Isolation of a Miller‐Dieker lissencephaly gene containing G protein beta‐subunit‐like repeats. Nature 1993: 364: 717–721.
[2]
Dobyns, W. B., Truwit, C. L., Ross, M. E., Matsumoto, N., Pilz, D. T., Ledbetter, D. H., Gleeson, J. G., Walsh, C. A., Barkovich, A. J. Differences in the gyral pattern distinguish chromosome 17-linked and X-linked lissencephaly. Neurology 1999; 53: 270-277.
[3]
Chong SS, Pack SD, Roschke AV, Tanigami A, Carrozzo R, Smith AC, Dobyns WB, Ledbetter DH. A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3. Hum Mol Genet 1997; 6: 147–155.
[4]
Lo Nigro, C., Chong, S. S., Smith, A. C. M., Dobyns, W. B., Carrozzo, R., Ledbetter, D. H. Point mutations and an intragenic deletion in LIS1, the lissencephaly causative gene in isolated lissencephaly sequence and Miller-Dieker syndrome. Hum. Molec. Genet. 1997; 6: 157-164. Blazejewski SM, Bennison SA, Smith TH and Toyo-oka K. Neurodevelopmental Genetic Diseases Associated With Microdeletions and Microduplications of Chromosome 17p13.3. Front. Genet 2018; 9: 80.
[5]
Pollin, T. I., Dobyns, W. B., Crowe, C. A., Ledbetter, D. H., Bailey-Wilson, J. E., Smith, A. C. M. Risk of abnormal pregnancy outcome in carriers of balanced reciprocal translocations involving the Miller-Dieker syndrome (MDS) critical region in chromosome 17p13.3. Am. J. Med. Genet 1999; 85: 369-375.
[6]
Shaffer, L. G. et al. An International System for Human Cytogenetic Nomenclature. Basel: Karger 20132016.
[7]
Kato, M., Dobyns, W. B. Lissencephaly and the molecular basis of neuronal migration. Hum. Molec. Genet. 12 (R1) 2003; R89-R96.
[8]
Fry AE, Cushion TD, Pilz DT. The genetics of lissencephaly. Am J Med Genet Part C Semin Med Genet, 2014, 166C: 198–210.
[9]
Cardoso, C., Leventer, R. J., Dowling, J. J., Ward, H. L., Chung, J., Petras, K. S., Roseberry, J. A., Weiss, A. M., Das, S., Martin, C. L., Pilz, D. T., Dobyns, W. B., Ledbetter, D. H. Clinical and molecular basis of classical lissencephaly: mutations in the LIS1 gene (PAFAH1B1). Hum. Mutat 2002; 19: 4-15.
[10]
Cardoso, C., Leventer, R. J., Ward, H. L., Toyo-oka, K., Chung, J., Gross, A., Martin, C. L., Allanson, J., Pilz, D. T., Olney, A. H., Mutchinick, O. M., Hirotsune, S., Wynshaw-Boris, A., Dobyns, W. B., Ledbetter, D. H. Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3. Am. J. Hum. Genet 2003; 72: 918-930.
[11]
Pilz, D. T., Matsumoto, N., Minnerath, S., Mills, P., Gleeson, J. G., Allen, K. M., Walsh, C. A., Barkovich, A. J., Dobyns, W. B., Ledbetter, D. H., Ross, M. E. LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation. Hum. Molec. Genet. 7 1998; 2029-2037.
[12]
Thomas MA, Duncan AM, Bardin C, Kaloustian VM. Lissencephaly with der(17)t(17;20)(p13.3; p12.2)mat. Am J Med Genet A 2004; 124A: 292-5.
[13]
Van Zelderen-Bhola SL, Breslau-Siderius EJ, Beverstock GC, Stolte-Dijkstra I, de Vries LS, Stoutenbeek P, et al. Prenatal and postnatal investigation of a case with Miller-Dieker syndrome due to a familial cryptic translocation t(17;20) (p13.3; q13.3) detected by fluorescence in situ hybridization. Prenat Diagn 1997; 17: 173-9.
[14]
Grosso S, Fichera M, Galesi O, Luciano D, Pucci L, Giardini F, et al. Bilateral periventricular nodular heterotopia and lissencephaly in an infant with unbalanced t(12;17)(q24.31; p13.3) translocation. Dev Med Child Neurol 2008; 50: 473-6.
[15]
Pollin TI, Dobyns WB, Crowe CA, Ledbetter DH, Bailey-Wilson JE, Smith AC. Risk of abnormal pregnancy outcome in carriers of balanced reciprocal translocations involving the Miller-Dieker syndrome (MDS) critical region in chromosome 17p13.3. Am J Med Genet 1999: 85: 369–375.
Browse journals by subject