Diagnosis of FSHD Type 1A Chromosome-4-Linked
Facioscapulohumeral Muscular Dystrophy 1A; FSHMD1A
Facioscapulohumeral muscular dystrophy type 1A (FSHD1A or FSHMD1A) is the more common form of FSHD. A conservative estimate of incidence is 1 in 14,000 births throughout the world; however, due to increased experience with FSHD, population-based research and improved genetic testing, this estimate may be low; actual incidence may be 1 in 7,500. In FSHD1A the disease is associated by genetic testing with the deletion of 3.3-kb repeats from a chromosomal tandem repeat called D4Z4 located near the end of chromosome 4 at the 4q35-qter location.
The D4Z4 region is a polymorphic variable number tandem repeat (VNTR) array consisting of 3.3 kb units. Unaffected individuals have a chromosome 4 D4Z4 array that has a span of 11 to 150 contiguous units. In individuals with FSHD, the chromosome 4 D4Z4 repeat array is contracted to a range between 1 to 10 contiguous units. Over time and through evolution the D4Z4 repeat array propagated to other parts of the human genome. D4Z4 is also present on the sub-telomere of chromosome 10. However, a shortened D4Z4 repeat on 10q26 does not cause FSHD.
Additionally, it is currently thought that a short array caused by the deletion of the D4Z4 region on chromosome 4q35 alone does not cause FSHD. Going towards the end of the chromosome beyond (distal to) the D4Z4 region, a specific genetic sequence has been identified as being needed to cause FSHD. Genetic variations of this type are called allelic subtypes or specificities; this particular variation is called allele type 4qA and 4qB. The two alleles are equally distributed in the entire population. Interestingly, patients with FSHD carry the 4qA variant in parallel to the shortened D4Z4 repeat region. Individuals who have a shortened D4Z4 array and a 4qB allele are unaffected for FSHD. The defining genetic feature that distinguishes the two allelic variants is the presence of a 6.2 kilobase β-satellite repeat on the 4qA allele.
The online database Online Mendelian Inheritance in Man (OMIM) is an excellent source for further information on the science and medicine of FSHD 1A. OMIM was designed for use by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. OMIM is developed and maintained by the National Center for Biotechnology Information (NCBI). This database is a catalog of human genes and genetic disorders and has hyperlinks to MEDLINE and sequence records in the Entrez system, and links to additional related resources at NCBI and elsewhere.
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