Molecular diagnosis of fragile x syndrome

Abstract

Sindrom fragilnog X-kromosoma jedan je od najčešćih nasljednih oblika mentalne retardacije, a nasljeđuje se X-vezano dominantno sa nepotpunom penetrantnošću. Kliničkom slikom dominira blagi do težak oblik mentalne retardacije, ali se javljaju i neke anatomske anomalije kao što su velika lubanja, dugo lice, izbočeno čelo, klempave uši, makroorhidizam te poremećaji ponašanja. Uzrok bolesti je povećan broj trinukleotidnih CGG ponavljanja na FMR-1 genu u kromosomskoj regiji Xq27.3. Specifično liječenje za ovu bolest za sada ne postoji. Cilj rada bio je utvrditi učestalost i dužinu ponavljanja CGG tripleta kod pojedinaca sa sumnjom na sindrom fragilnog X-kromosoma čiji su uzorci krvi testirani u KBC-u Zagreb u vremenskom periodu od 2004. do 2015. godine. Podaci su prikupljeni iz medicinske dokumentacije i obrađeni deskriptivnom statistikom. Analizom 1602 uzorka elektroforezom na gelu utvrđen je normalni broj ponavljanja tripleta CGG (5-54) u 1505 uzoraka (94%), broj uzoraka s premutacijama (55-200 CGG tripleta) iznosio je 41 (2%), a broj uzoraka s punom mutacijom (>200 CGG ponavljanja) iznosio je 56 (4%).Fragile X syndrome is one of the most common X-linked dominant inherited form of mental retardation. It results in a spectrum of intellectual disabilities ranging from mild to severe as well as physical characteristics such as an elongated face, large or protruding ears, and large testicles (macroorchidism), and behavioral characteristics such as stereotypic movements and social anxiety. Fragile X syndrome is associated with the expansion of the CGG trinucleotide repeat affecting the Fragile X mental retardation 1 (FMR-1) gene on the X chromosome, resulting in a failure to express the fragile X mental retardation protein (FMRP), which is required for normal neural development. The selective therapy for fragile X syndrome is still non-existent. The aim of the study has been to determine the frequency and the extension of CGG trinucleotide repeats in individuals suspected of having fragile X syndrome whose blood samples were tested in UHC Zagreb in time period from 2004 to 2015. The data for this study has been gathered from medical documentation and analysed by descriptive statistics. Through the analysis of 1602 blood samples by gel electrophoresis, the normal amount of CGG trinucleotide repeat (5-54) was found in 1505 samples (94%), the number of samples with premutation (55-200 CGG trinucleotide repeat) was found in 41 patients (2%), and the number of samples with full mutation (>200 CGG trinucleotide repeat) was found in 56 patients (4%)