1022-7954/03/3902- $25.00 © 2003
Russian Journal of Genetics, Vol. 39, No. 2, 2003, pp. 147–151. Translated from Genetika, Vol. 39, No. 2, 2003, pp. 202–206.
Original Russian Text Copyright © 2003 by Petrov, Laoudj, Vassetzky.
Fascioscapulohumeral muscular dystrophy, or
Landouzy–Dejerine disease (FSHD), is a hereditary
neuromuscular disorder ranking third in prevalence
after Duchenne muscular dystrophy and myotonic dys-
trophy. The age at onset of clinical signs varies from
early childhood to rather advanced age, but typically
the disease starts in adolescence. In general case, the
disease initially affects the facial muscles (only the
mimic muscles, and not the masticatory, temporal, pha-
ryngeal, and oculomotor muscles) and the shoulder gir-
dle muscles. Subsequently, the femoral and foot mus-
cles become affected. The typical features of the dis-
ease are marked asymmetry of muscular development
(of the left and right body sides) and the thinness of bul-
bar extraocular and respiratory muscles .
Numerous investigations, which were initiated as
early as in 1885 by a study of Landouzy and Dejerine
, showed that the disease had autosomal dominant
mode of inheritance. The FSHD frequency is about two
cases per one million of the population . The birth
rate in the patients is somewhat diminished, and the
mutation rate does not exceed ﬁve per ten million
Beginning from 1985, many investigations were
focused on mapping of the FSHD locus . First, it was
found that there was an association between FSHD and
the Mfd22 microsatellite marker on chromosome 4 .
Mapping of this marker helped to localize the FSHD
locus within telomeric region of chromosome 4q.
Using in situ hybridization, another marker, D4S139,
also shown to be associated with FSHD, was mapped to
region 4q35-gter .
In 1992, using a combination of classical restriction
fragment length polymorphism and PCR-polymor-
phism methods, a detailed map of the telomeric region
of the long arm of chromosome 4 was constructed. This
helped determination of the gene marker order within
the 4q35 region . All patients with a conﬁrmed diag-
nosis of FSHD carry a chromosomal rearrangement
within the subtelomeric region of chromosome 4q
(4q35). This subtelomere, termed D4Z4, is composed
of a polymorphic repeat structure consisting of 3.3-kb
repeated elements . The number of repeat units var-
ies from 10 to more than 100 in the population, whereas
in the FSHD patients, the number of these units is sub-
stantially diminished (to 1–10) because of the deletion
of an integral number of the repeats. Mapping experi-
ments showed that the rearrangement occurred in locus
4q35 distal to D4S139 (Fig. 1). This defect is caused by
the reduction of the number of telomeric repeats in the
locus 4q35, most likely because of homologous recom-
bination between the repeats on chromosomes 4 and 10
STRUCTURE OF THE 4q35 LOCUS
AND D4Z4 REPEAT
Analysis of the D4Z4 nucleotide sequence showed
that each repeat unit contained two homeoboxes and
Genetics and Epigenetics
of Progressive Fascioscapulohumeral (Landouzy–Dejerine)
, D. Laoudj
, and Ye. Vassetzky
Moscow State University, Moscow, 119899 Russia
Centre National de la Recherche Scientiﬁque, UMR-8126, Villejuif, F-94805 France; e-mail: firstname.lastname@example.org
Institute of Human Genetics, Montpellier F-34986, France
Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 117808 Russia
Received October 4, 2002
—Landouzy–Dejerine muscular dystrophy is a rare hereditary disease with prevalence of 0.9 to 1.4 in
100 000. Clinically the disease is characterized by weakness and atrophy of the facial and shoulder girdle mus-
cles. It is caused by partial deletion of the 3.3-kb subtelomeric D4Z4 repeat on chromosome 4 (locus 4q35).
This paper presents a critical review of the literature data and hypotheses explaining molecular mechanisms of
progressive fascioscapulohumeral muscular dystrophy.
D4Z4 TUB 4q FRG1FRG2
Structure of the 4q35 locus containing D4Z4 repeat.