Fragile X Syndrome at the FRAXE Locus: Clinical and Molecular Genetics Diagnosis of Affected Family
1; K. Světnicová
2; Š. Mašková
2; P. Hněvsová
3; G. Křečková
4; L. Kozák
Centrum molekulární biologie a genové terapie, IHOK, Fakultní nemocnice Brno
přednosta prof. MUDr. J. Vorlíček, CSc.
1; Oddělení lékařské genetiky, Fakultní Thomayerova nemocnice, Praha
primář MUDr. V. Gregor
2; Oddělení dětské neurologie, Fakultní Thomayerova nemocnice, Praha
primář MUDr. J. Hadač, CSc.
3; Gennet CZ, s. r. o., pobočka Liberec
primář MUDr. D. Stejskal
Čes-slov Pediat 2007; 62 (11): 638-643.
Fragile X syndrome is X linked inherited disease which manifests with mental retardation at affected males and mild mental dysfunction at affected females. Majority of patients have also behavioral problems including hyperactivity and autism. There are two different types of fragile X syndrome on the molecular level: FRAXA and FRAXE. Present article deal with clinical and molecular genetics analysis of affected family for the FRAXE type of fragile X syndrome that has not been described in the Czech literature yet.
First, the FRAXA type of syndrome was excluded by molecular analysis at the proband with psychomotor retardation. Consecutively, a method for detection of the FRAXE type of syndrome was established by combination of polymerase chain reaction (PCR) and Southern blotting. Described technique allows to determine an expansion and approximate size of (CCG)n repeat at the 5’ end of the FMR2 gene. It was found that mother of the proband is a carrier of the mutant FRAXE allele which passed to her son. In agreement with previously published results, it was confirmed that the (CCG)n repeat at the FMR2 gene is unstable when passed through one generation to the next.
Both, the expansion and the contraction of the (CCG)n repeat was observed at studied family. Our report indicates that not only DNA analysis of FMR1 gene (FRAXA type) but also DNA analysis of FMR2 gene (FRAXE type) is important at patients with mental retardation that are suspected for fragile X syndrome.
fragile X syndrome, FRAXA, FRAXE, mental retardation, DNA diagnosis
General practitioner for children and adolescents