中華民國小兒科醫學會第137屆學術演講會教育演講：先天性畸形－易脆X染色體徵候群

Abstract

The fragile X syndrome is the most common inherited form of mental retardation. second only to Down syndrome, which is usually sporadic and not inherited. The condition segregates a X-linked dominant disorder with incomplete penetrance. Fully penetrant males exhibit moderate mental retardation along with a phenotype consisting of macro-orchidism (enlarged testes), substle facial dysmorphia, and mild connective tissue abnormalities. Female patients typically are less severely affected, showing little or no somatic signs and only borderline to mild mental retardation. The prevalence of affected male has been estimated approximately 1/1250, while that of nonpenetrant males has been estimated as 1/5000, leading to an overall prevalence of about 1/1000 among males. Among female carriers, approximately onethird havc some evidence of mental impairment or mental retardation The population prevalence of affected females is approximately 1/2000. Thus the overall prevalence of female carriers is estimiated to be about 1/700. On the basis of these estimates, it apperas that about 1/850 people carry the fra (X) chromosome. The vast majority of patients with the fragile X syndrome show a folate-sensitive fragile site at Xq27.3 (FRAXA) at thc cytogenetic level, and both amplification of the p (CGG) n repeat and hypermethylation of the CpG island in the S fragile X genc (FMRI) at the molecular level. The absence of FMRI message and its encoded protein FMRP is believed responsible for the phenotype of the fragile X syndrome. In addition to the common mutation change of repeat expansion, three variant patients with the clinical presentation of fragile X syndrome have been reported: two males with large deletions encompassing the FMRI locus and a severely affected male with a FMRI, lie^367→Asn missense mutation. The dynamic mutations caused by expanding trinucleotide repeats turned to be common causes of human disease. In the past two years they have been fingered as the culprits in three hereditary disorders besides fragile X syndrome: myotonic dystrophy. spinaobulbar muscular atrophy and Huntinton's disease. All in all, The trinucleotide repeat expansions have shaken the field of genetics almost as much as did Barbara McClintock's jumping genes, or transposons.