Esra KILIÇ

Mikrosefali ile İlişkili Genetik Faktörler

Mikrosefali bir hastalık değildir, bir klinik bulgudur ve öğrenme güçlüğü ile sıklıkla ilişkili olan azalmış intrakranyal beyinhacmini tahmin etmemizi sağlar. İntrauterin nöronal gelişimdeki anormal süreç primer mikrosefaliye sebep olur. Sekondermikrosefali doğumdan sonra gelişir ve sıklıkla beyaz cevher hastalıkları ile ilişkilidir. Mikrosefalinin altında yatan etyolojiksebepler kompleks veya multifaktöriyel olabilir. Bu sebepler, anormal mitotik iplikcik yapısı, anormal sentrozomal proteinyapısı, bozuk siliyer fonksiyon, bozuk DNA tamir mekanizması ve replikasyon bozukluklarını içerir. Biz burada primerkonjenital ve sekonder gelişimsel mikrosefalinin genetik faktörlerini gözden geçireceğiz.

Genetic Disorders Associated with Microcephaly

Microcephaly, is not a disease, is a clinical finding and a simple assessment of decreased intracranial brain volume which is frequently associated with intellectual disability. Abnormal developmental processes which affects in utero neuron development results primary microcephaly at birth. The secondary microcephaly develops after birth and mostly associated with white matter diseases. The underlying etiologies of microcephaly are complex and multifactorial. These include abnormal mitotic spindle structure, centrosomal protein abnormalities, impaired cilia function, damaged DNA repair mechanism and DNA replication. Here we overview the genetic factors of primer congenital and secondary developmental microcephaly.

PDF

___

1. Opitz JM, Holt MC. Microcephaly: general considerations and aids to nosology. J Cranio fac Genet Dev Biol 1990; 10: 175-204.
2. Woods CG, Parker A. Investigating microcephaly. Arch Dis Child 2013; 98: 707-713.
3. Gilbert SL, Dobyns WB, Lahn BT. Genetic links between brain development and brain evolution. Nat Rev Genet 2005; 6: 581- 90.
4. Alcantara D, O’Driscoll M. Congenital microcephaly. Am J Med Genet C Semin Med Genet 2014; 166C: 124-39.
5. Elçioğlu, H. Nursel; Salim, Mahmoud. Mikrosefali. Turkiye Klinikleri Journal of Pediatrical Sciences, 2013; 9: 39-46.
6. Abdel-Hamid MS, Ismail MF, Darwish HA, Effat LK, Zaki MS, AbdelSalam GM. Molecular and phenotypic spectrum of ASPM-related primary microcephaly: Identification of eight novel mutations. Am J Med Genet Part A 2016; 170: 2133-40.
7. Thornton GK, Woods CG. Primary microcephaly: do all roads lead to Rome? Trends Genet 2009; 25: 501-10.
8. He H, Liyanarachchi S, Akagi K,Nagy R, Li J, Dietrich RC, et al. Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I. Science 2011; 332: 238-40.
9. Rauch A. The shortest of the short: pericentrin mutations and beyond. Best Pract Res Clin Endocrinol Metab 2011; 25: 125-30.
10. Willems M, Geneviève D, Borck G,Baumann C, Baujat G, Bieth E, et al. Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families. J Med Genet 2010; 47:797-802.
11. Ütine GE, Şimşek-Kiper PÖ, Boduroğlu K. Mikrodelesyon sendromları. Çocuk Sağlığı ve Hastalıkları Dergisi 2012; 55: 42- 51.
12. Schrier SA, Sherer I, Deardorff MA,Clark D, Audette L, Gillis L,et al. Causes of death and autopsy findings in a large study cohort of individuals with Cornelia de Lange syndrome and review of the literature. Am J Med Genet A 2011;155: 3007-24.
13. de Munnik SA, Bicknell LS, Aftimos S,Al-Aama JY, van Bever Y, Bober MB, et al. Meier-Gorlin syndrome genotype-phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis. Eur J Hum Genet 2012; 20: 598-606.
14. Kato M, Dobyns WB. Lissencephaly and the molecular basis of neuronal migration. Hum Mol Genet 2003;12: 89-96.
15. Hennekam RC. Rubinstein-Taybi syndrome. Eur J Hum Genet 2006;14:981-5.
16. Ashwal S, Michelson D, Plawner L, Dobyns WB; Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Practice parameter: Evaluation of the child with microcephaly (an evidencebased review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2009; 73: 887-97.
17. Seltzer LE, Paciorkowski AR. Genetic disorders associated with postnatal microcephaly. Am J Med Genet C Semin Med Genet 2014;166C:140-55.
18. Nowaczyk MJ, Irons MB. Smith-Lemli-Opitz syndrome: phenotype, natural history, and epidemiology. Am J Med Genet C Semin Med Genet 2012;160C:250-62.
19. Garavelli L, Mainardi PC. Mowat-Wilson syndrome. Orphanet J Rare Dis 2007; 24; 2:42.