Close linkage of fragile X-mental retardation syndrome to haemophilia B and transmission through a normal male

• Published in: Nature (London) 1983-12, Vol.306 (5944), p.701-704
• Main Authors: Camerino, G, Mattei, M. G, Mattei, J. F, Jaye, M, Mandel, J. L
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Alleles; Biological and medical sciences; Child; Child, Preschool; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); DNA - metabolism; Factor IX - genetics; Female; Genes; Hemophilia A - complications; Hemophilia A - genetics; Humanities and Social Sciences; Humans; Infant; Intellectual Disability - complications; Intellectual Disability - genetics; letter; Male; Medical genetics; Medical sciences; Middle Aged; multidisciplinary; Pedigree; Science; Science (multidisciplinary); Sex Chromosome Aberrations; X Chromosome
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/306701a0

The fragile X-mental retardation syndrome 1 is defined by a moderate to severe mental retardation associated with a cytogenetic marker, a fragile site localized on the long arm of the X chromosome at band Xq 27 (ref. 2). This syndrome has recently been recognized as one of the major causes of genetically determined mental retardation, and as one of the most important X-linked diseases with respect to its frequency (analogous to that of Duchenne muscular dystrophy or of haemophilia A) and severity 3–6 . In the absence of treatment, genetic screening for this disease would seem particularly important. Prenatal diagnosis is now feasible although difficult 7,8 and detection of heterozygous carriers is only possible in ∼50% of cases 1,4,9 . The recent demonstration of genetic linkage between the glucose 6-phosphate dehydrogenase (G6PD)–colour blindness cluster (at Xq28) and the fragile X locus has suggested that the fragile site is indeed the site of the mutation 10 . We show here that the fragile X and haemophilia B loci are closely linked, using as genetic marker a polymorphism of the coagulation factor IX gene 11 . Our study of a large family has demonstrated transmission through a phenotypically normal male, a feature previously described in retrospective analysis of a few other fragile X pedigrees 1,6,12,13 . Restriction polymorphisms associated with the factor IX gene should be useful for analysing this peculiar aspect of the genetics of the fragile X syndrome, and for genetic screening of the disease.