부산대학교 도서관

INTRODUCTION Holoprosencephaly (HPE, #MIM 236100), resulting from failed forebrain separation during early embryogenesis, is the most common developmental defect in humans with an incidence of 1:250 in first trimester fetuses [...]
Objective: Holoprosencephaly (HPE, #MIM 236100) is the most common developmental defect of midline cleavage in the human forebrain. Environmental, genetic, and multifactorial causes are involved in its etiology. About half of the cases have chromosome aberrations such as trisomies 13 and 18, triploidy and structural imbalances. Single gene mutations have been shown in ~25% of cases. In this retrospective study, we aimed to determine the etiological factors related to HPE in 127 fetuses. Material and Method: This study comprises 127 prenatally diagnosed fetal HPE samples from a period of 25 years, which were evaluated by karyotyping, fluorescence in situ hybridization (FISH) and aCGH investigation. Results: A total of 64 (50.39%) chromosome aberrations were identified in this cohort. The predominant chromosomal abnormality was trisomy 13 (n=38), which was followed by trisomy 18 (n=8) and triploidy (n=5). Terminal 7q deletion was the most frequent structural anomaly (n=10, of which 5 were de novo deletion, 4 were an unbalanced product of maternal translocations and one unknown in origin) and the deletion of 18p was detected in one case. In the remaining two cases, we detected trisomy 20 and pericentric inversion 11 coincidentally. Conclusion: This study, indicates that in the presence of clinical findings suggesting HPE, cytogenetic and molecular cytogenetic studies should be performed. An aCGH study must also be done for submicroscopic chromosomal anomalies, to determine their sizes, real breakpoints and identify possible novel genes that might play a role in HPE etiology. Keywords: Holoprosencephaly, HPE, #MIM 236100, nervous system malformations, prenatal diagnosis Amac: Holoprosensefali (HPE, #MIM 236100), on beyin orta hat bolunmesinde en sik gorulen gelisimsel bozukluktur. Etiyolojisinde, cevresel, genetik ve multifaktoriyel hastaliklar rol oynamaktadir. Vakalarin yaklasik yarisinda, trizomi 13 basta olmak uzere, trizomi 18 ve triploidi gibi sayisal anomaliler ve yapisal kromozom anomalileri bulunmaktadir. Olgularin ~%25'inde tek gen mutasyonlari gosterilmistir. Bu retrospektif calismada fetal donemde saptanan 127 fetuste HPE etiyolojisinde rol oynayan faktorlerin arastirilmasi planlandi. Gerec ve Yontem: Bu calisma, 25 yillik bir periyotta fetal ultrasonografide HPE tanisi konmus 127 fetusta yapilan klasik karyotipleme, floresan in situ hibridizasyon (FISH) ve aCGH incelemelerinin sonuclarini icermektedir. Bulgular: Bu kohortta olgularin 64 (%50,39)'unde bir kromozom anomalisi tespit edildi. En sik gorulen sayisal kromozomal anomali beklendigi gibi trizomi 13 (n=38) idi, bunu sirasiyla trizomi 18 (n=8) ve triploidi (n=5) izlemistir. Yapisal kromozom anomalilerinden terminal 7q delesyonu en sik gorulen anomaliydi (n=10, 5'i de novo, 4'u maternal translokasyonun dengesiz urunu, 1 olgunun kokeni ise bilinmiyordu). Bir olguda 18. kromozomun p kolunda bir delesyon saptandi. Kalan 2 olguda tesadufi olarak trizomi 20 ve 11. kromozomda perisenttrik bir inversiyon saptandi. Sonuc: Bu calisma, HPE klinik bulgularin varliginda sitogenetik ve molekuler sitogenetik calismalarin birlikte veya tamamlayici olarak yapilmasi gerektigini gostermektedir. Ozellikle aCGH ca lismasi submikroskopik yapisal kromozomal anomalilerin boyutlarini ve kirik noktalarini, bolgede yer alan genleri belirlemekte oldugu kadar HPE etiyolojisinde rol oynayabilecek olasi yeni genleri tanimlamak icin de yapilmalidir. Anahtar Kelimeler: Holoprosensefali, HPE, #MIM 236100, merkezi sinir sistemi, prenatal tani