Otizm genetiği

Otizm merkezi sinir sisteminin gelişimsel bir bozukluğudur. Günümüze kadar etiyolojisi tam olarak saptanamamıştır. Otizmin bazı tipleri tek başına veya genetik sendromun bir parçası olarak kalıtsal olmakla birlikte bir kısmı çevresel faktörler ile ortaya çıkmaktadır. Günümüze kadar yapılan aile ve ikiz çalışmaları hastalığın etiyolojisinde genetik faktörlerin önemli bir rol oynadığını göstermiştir. Hastalığın hem lokus hem de allelik heterojenite gösterdiği, kalıtım tipinin ise eşik değerli multifaktöryel kalıtım modeli ile uygunluk gösterdiği saptanmıştır. Günümüzde otizm genetiğiyle ilgili, kromozom anomalilerinin incelenmesi, ilişki çalışmaları ve genetik bağlantı analiz çalışmaları hızlı bir şekilde devam etmektedir. Otistik olgularda hem yapısal hem de sayısal çok sayıda kromozom anomalisi bildirilmiştir. İlişki ve genetik bağlantı çalışmalarında hasta seçme kriterlerinin farklı olması, farklı genetik markırların kullanılması, genetik harita ve istatistik analizlerinin değişkenliğinden dolayı farklı sonuçlar bulunmuştur. Bununla birlikte 7 kromozom bölgesinde (2, 3, 7, 11, 15, 17, X kromozomları) maksimum Lod skor anlamlı bulunmuştur. Günümüzde otistik hastalarda, kromozom 3'te GAT1 ve OXTR, kromozom 7'de FOXP2, WNT2, RELN, HOXA1 ve HOXB1, kromozom 11'de HRAS, kromozom 15'de GABRB3, GABRA5, GABRG3, UBE3A ve ATP10C, kromozom 17'de 5-HTT, kromozom X'de MeCP2, NLGN3 ve NLGN4 genlerinde çeşitli değişiklikler saptanmış olup bu genler üzerinde yoğun çalışmalar sürmektedir.

A genetics of autism

Background and Design.- Autism is a complex neurodevelopmental disorder. Etiology has not been clearly noticed up to date. Although some types of autism are hereditary on their own or as part of genetic syndrome, the others emerge from environmental factors Family and twin studies have shown that genetic factors are significant in the disease's etiology. The disease was noticed to show both locus and allelic heterogeneity. The researches offered the most evidence for combined many additive genes and environmental factors in absence of major gene effect. This suggested a multifactorial threshold model. Today various studies (chromosome anomalies, genetic linkage analysis, assosiation studies) on autism are being done to notice the sensitive genes. Up to date a number of both structural and numerial chromosome anomalies have been reported. Due to the fact that patient selection criteria were different, different genetic markers were used and map and statistic analysis were changeable, the results varied. Neverthless maximum Lod score in 2, 3, 7, 11, 15, 17andX chromosomes was found significant. Intensive studies are done on following genes, GAT1 and OXTR on chromosome 3, FOXP2,WNT2,RELN,HOXA1 and HOXB1 on chromosome 7, HRAS on chromosome 11, GABRB3, GABRA5, GABRG3, UBE3A and ATP10C on chromosome 15, 5-HTT on chromosome 17, MeCP2, NLGN3 and NLG4 on chromosome X.

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