Zeynep OCAK, Ergin IŞIK, Behzat ÖZKAN, Ahmet YEŞİLYURT, Sıtkı ÖZTAŞ, Hakan DONERAY, Abdulgani TATAR

Seckel Syndrome with Spontaneous Chromosomal Instability

Seckel syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth retardation, bird-headed face and mild mental retardation. It is a disorder involving the DNA damage-response genes. Failure in the DNA damage response and repair process can cause chromosomal instability. In addition, it is possible that there are several loci responsible for this syndrome, and variety in the molecular pathogenesis is the cause of phenotypic heterogeneity. Three different loci have been reported thus far. The effect of the locus with mutation on phenotype may be used in the subgrouping of Seckel syndrome. We report a case with Seckel syndrome having spontaneous chromosomal instability. The patient had no hematologic or malignant disease although there was a severe chromosomal instability. To date, spontaneous chromosomal instability has been reported in two cases with Seckel syndrome.

Anahtar Kelimeler:

Seckel syndrome, chromosomal instability, chromosomal breakage syndrome

Seckel Syndrome with Spontaneous Chromosomal Instability

Keywords:

Seckel syndrome, chromosomal instability, chromosomal breakage syndrome,

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1. Faivre L, Merrer ML, Lyonnet S, Plauchu H, Dagoneau N, CamposXavier AB et al. Clinical and genetic heterogeneity of Seckel syndrome. Am J Med Genet 2002; 112: 379-83.
2. Chanan-Khan A, Holkova B, Perle MA, Reich E, Wu CD, Inghirami G et al. T-cell clonality and myelodysplasia without chromosomal fragility in a patient with features of Seckel syndrome. Haematologica 2003; 88: ECR14.
3. Shanske A, Caride DG, Menasse-Palmer L, Bogdanow A, Marion RV. Central nervous system anomalies in Seckel syndrome: report of a new family and review of the literature. Am J Med Genet 1997; 70: 155-8.
4. Woods CG, Leversha M, Rogers JG. Severe intrauterine growth retardation with increased mitomycin C sensitivity: a further chromosome breakage syndrome. J Med Genet 1995; 32: 301- 5.
5. Butler MG, Hall BD, Maclean RN, Lozzio CB. Do some patients with Seckel syndrome have hematological problems and/or chromosome breakage? Am J Med Genet 1987; 27: 645-9.
6. Rooney DE, Czepulkowski BH. Human cytogenetics: a practical approach. 1st ed. Oxford: IRL Press Ltd; 1986.
7. Goodship J, Gill H, Carter J, Jackson A, Splitt M, Wright M. Autozygosity mapping of a Seckel syndrome locus to chromosome 3q22.1-q24. Eur J Hum Genet 2001; 9: 753-7.
8. Casper AM, Durkin SG, Arlt MF, Glover TW. Chromosomal instability at common fragile sites in Seckel syndrome. Am J Hum Genet 2004; 75: 654-60.
9. Silengo M, Del Monaco A, Linari A, Lala R. Low birth-weight, microcephalic malformation syndrome in a 46,XX girl and her 46,XY sister with agonadism: third report of the Kennerknecht syndrome or autosomal recessive Seckel-like syndrome with previously undescribed genital anomalies. Am J Med Genet 2001; 101: 275-8.
10. Sugio Y, Tsukahara M, Kajii T. Two Japanese cases with microcephalic primordial dwarfism: classical Seckel syndrome and osteodysplastic primordial dwarfism type II. Jpn J Hum Genet 1993; 38: 209-17.
11. Bobabilla-Morales L, Corona-Rivera A, Corona-Rivera JR, Buenrostro C, Garcia-Cobian TA, Corona-Rivera E et al. Chromosome instability induced in vitro with mitomycin C in five Seckel syndrome patients. Am J Med Genet 2003; 123: 148-52.
12. Syrrou M, Georgiou I, Paschopoulos M, Lolis D. Seckel syndrome in a family with three affected children and hematological manifestations associated with chromosome instability. Genet Couns 1995; 6: 37-41.
13. Borglum AD, Balslev T, Haagerup A, Birkebaek N, Binderup H, Kruse TA et al. A new locus for Seckel syndrome on chromosome 18p11.31-q11.2. Eur J Hum Genet 2001; 9: 753-7.
14. Kilinc MO, Ninis VN, Ugur SA, Tuysuz B, Seven M, Balci S et al. Is the novel SCKL3 at 14q23 the predominant Seckel locus? Eur J Hum Genet 2003; 11: 851-7.
15. O'Driscoll M, Ruiz-Perez VL, Woods CG, Jeggo PA, Goodship JA. A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat Genet 2003; 33: 497-501.