TY - JOUR
T1 - Contractions of D4Z4 on 4qB subtelomeres do not cause facioscapulohumeral muscular dystrophy
AU - Lemmers, Richard J.F.L.
AU - Wohlgemuth, Mariëlle
AU - Frants, Rune R.
AU - Padberg, George W.
AU - Morava, Eva
AU - Van Der Maarel, Silvère M.
N1 - Funding Information:
This research was made possible by the Prinses Beatrix Fonds, the Stichting Spieren voor Spieren, the Muscular Dystrophy Association USA, the FSH Society, the Stichting FSHD, the Shaw family, and the National Institutes of Health.
PY - 2004/12
Y1 - 2004/12
N2 - Facioscapulohumeral muscular dystrophy (FSHD) is associated with contractions of the D4Z4 repeat in the subtelomere of chromosome 4q. Two allelic variants of chromosome 4q (4qA and 4qB) exist in the region distal to D4Z4. Although both variants are almost equally frequent in the population, FSHD is associated exclusively with the 4qA allele. We identified three families with FSHD in which each proband carries two FSHD-sized alleles and is heterozygous for the 4qA/4qB polymorphism. Segregation analysis demonstrated that FSHD-sized 4qB alleles are not associated with disease, since these were present in unaffected family members. Thus, in addition to a contraction of D4Z4, additional cis-acting elements on 4qA may be required for the development of FSHD. Alternatively, 4qB subtelomeres may contain elements that prevent FSHD pathogenesis.
AB - Facioscapulohumeral muscular dystrophy (FSHD) is associated with contractions of the D4Z4 repeat in the subtelomere of chromosome 4q. Two allelic variants of chromosome 4q (4qA and 4qB) exist in the region distal to D4Z4. Although both variants are almost equally frequent in the population, FSHD is associated exclusively with the 4qA allele. We identified three families with FSHD in which each proband carries two FSHD-sized alleles and is heterozygous for the 4qA/4qB polymorphism. Segregation analysis demonstrated that FSHD-sized 4qB alleles are not associated with disease, since these were present in unaffected family members. Thus, in addition to a contraction of D4Z4, additional cis-acting elements on 4qA may be required for the development of FSHD. Alternatively, 4qB subtelomeres may contain elements that prevent FSHD pathogenesis.
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U2 - 10.1086/426035
DO - 10.1086/426035
M3 - Article
C2 - 15467981
AN - SCOPUS:8844227430
SN - 0002-9297
VL - 75
SP - 1124
EP - 1130
JO - American journal of human genetics
JF - American journal of human genetics
IS - 6
ER -