вход по аккаунту



код для вставкиСкачать
American Journal of Medical Genetics 72:363–368 (1997)
Limb Girdle Muscular Dystrophy in Manitoba
Hutterites Does Not Map to Any of the Known
Tracey Weiler,1 Cheryl R. Greenberg,2,3 Edward Nylen,1 Kenneth Morgan,4,5 T. Mary Fujiwara,4,5,6
M. Joyce Crumley,4,5 Teresa Zelinski,2,3 William Halliday,7 Barbara Nickel,1
Barbara Triggs-Raine,1,2 and Klaus Wrogemann1,2,3*
Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Manitoba, Canada
Department of Human Genetics, University of Manitoba, Winnipeg, Manitoba, Canada
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
Departments of Human Genetics and Medicine, McGill University, Montreal, Quebec, Canada
Montreal General Hospital Research Institute, Montreal, Quebec, Canada
Department of Pediatrics, McGill University, Montreal, Quebec, Canada
Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada
Limb girdle muscular dystrophy (LGMD) is
a heterogeneous group of disorders affecting primarily the shoulder and pelvic
girdles. Autosomal dominant and recessive
forms have been identified; 8 have been
mapped and 1 more has been postulated on
the basis of exclusion of linkage. An autosomal recessive muscular dystrophy was first
described in 1976 in the Hutterite Brethren,
a North American genetic and religious isolate [Shokeir and Kobrinsky, 1976; Clin
Genet 9:197–202]. In this report, we discuss
the results of linkage analysis in 4 related
Manitoba Hutterite sibships with 21 patients affected with a mild autosomal recessive form of LGMD. Because of the difficulties in assigning a phenotype in some
asymptomatic individuals, stringent criteria for the affected phenotype were employed. As a result, 7 asymptomatic relatives
with only mildly elevated CK levels were assigned an unknown phenotype to prevent
their possible misclassification. Two-point
linkage analysis of the disease locus against
markers linked to 7 of the known LGMD loci
and 3 other candidate genes yielded lod
scores of <-2 at u=0.01 in all cases and in
Contract grant sponsors: Medical Research Council of Canada;
Muscular Dystrophy Association of Canada; Manitoba Medical
Services Foundation; Canadian Genetic Diseases Network; Winnipeg Rh Institute Foundation; Children’s Hospital of Winnipeg
Research Foundation.
*Correspondence to: Klaus Wrogemann, MD, PhD, Department of
Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, MB, Canada R3E 0W3. E-mail: [email protected]
Received 11 March 1997; Accepted 21 May 1997
© 1997 Wiley-Liss, Inc.
most cases at u=0.05. This suggests that
there is at least 1 additional locus for LGMD.
Am. J. Med. Genet. 72:363–368, 1997.
© 1997 Wiley-Liss, Inc.
KEY WORDS: LGMD; exclusion; limb girdle;
gene mapping; muscular dystrophy; Hutterite
To date, 9 separate loci for limb girdle muscular dystrophy (LGMD) have either been mapped through linkage analysis or postulated to exist by exclusion of linkage. Two autosomal dominant LGMD loci (LGMD1A
and LGMD1B) were mapped to chromosome regions
5q31-q33 [Speer et al., 1992; Yamaoka et al., 1994] and
1q11-q21 [Van der Kooi et al., 1997] respectively. Autosomal recessive loci (LGMD2A-2F) were mapped to 6
chromosome regions: 15q15.1-q21.1 [Allamand et al.,
1995], 2p13.3 [Passos-Bueno et al., 1995a], 13q12-q13
[Ben-Othmane et al., 1992; Ben Othmane et al., 1995],
17q12-q21.33 [Roberds et al., 1994], 4q12 [Bönnemann
et al., 1995; Lim et al., 1995], and 5q33-q34 [PassosBueno et al., 1996]; a 7th locus has been postulated to
exist by exclusion to known loci [Passos-Bueno et al.,
1996]. Recently, Miyoshi myopathy (MM) was mapped
to chromosome region 2p12-p14 [Bejaoui et al., 1995],
and we and others have suggested that mutations at
the LGMD2B locus cause both MM and LGMD2B
[Bejaoui et al., 1995; Weiler et al., 1996]. Genes have
been identified for 5 of the 6 autosomal recessive loci:
mutations in the gene encoding calpain 3 (CANP3)
cause LGMD2A [Richard et al., 1995]; and mutations
in the genes encoding 4 components of the sarcoglycan
complex (a-, b-, g- and d-sarcoglycan) cause LGMD2D
[Roberds et al., 1994], LGMD2E [Lim et al., 1995; Bön-
Weiler et al.
nemann et al., 1995], LGMD2C [Noguchi et al., 1995],
and LGMD2F [Nigro et al., 1996], respectively.
Here we report the exclusion of 7 of the known
LGMD loci as causing LGMD in 4 Canadian Hutterite
families with an autosomal recessive form of LGMD.
One of the patients included in this study was in the
original description of muscular dystrophy in the Hutterites [Shokeir and Kobrinsky, 1976] (MIM [254110).
Patients and Pedigree
We reconstructed a detailed pedigree on the basis of
information obtained from the initial publication
[Shokeir and Kobrinsky, 1976], Schmiedeleut family
records [Gross, 1996], our genealogical database (Fujiwara, Crumley, and Morgan, unpublished data), and
confirmatory interviews with the family (Fig. 1). Personal interviews and musculoskeletal examinations
were performed by CRG and consulting neurologists on
available relatives included in this study. Blood
samples were obtained from all consenting individuals
for DNA banking, Epstein Barr virus transformation,
creatine kinase (CK) analysis, and blood group serology. Electrophysiological studies, open muscle biopsies,
and echocardiographic assessments were performed
where feasible. Individuals were considered to be affected with LGMD if: (1) they exhibited signs and
symptoms of proximal muscle weakness with CK levels
ù4× normal in the absence of any other explanation for
CK elevation; (2) they exhibited signs and symptoms of
proximal muscle weakness and had a muscle biopsy
consistent with LGMD; or (3) their CK levels were
ù15× normal but they were asymptomatic. Individuals
were considered to be unaffected if they were symptomfree, had a normal musculoskeletal exam, and a normal
CK level. Individuals were assigned an unknown phe-
notype if their CK levels were > normal but ø4× normal and they were asymptomatic.
DNA Studies
DNA was extracted from whole blood as previously
described [Greenberg et al., 1987]. Oligonucleotide
primers designed to amplify 36 microsatellite loci
linked to 10 candidate loci, including DAG1, LGMD1A,
LGMD2F, SNT2B1, and SNT2B2 [Weber et al., 1991;
Ben-Othmane et al., 1992; Bashir et al., 1994; Fougerousse et al., 1994; Yamaoka et al., 1994; Allamand et
al., 1995; Passos-Bueno et al., 1995b; Lim et al., 1995;
Passos-Bueno et al., 1996], were obtained from Research Genetics, Inc. (Huntsville, AL). Markers linked
to LGMD1B were not tested because the location of this
disease gene only became known during review of this
paper. The chromosomal locations were obtained from
maps located in the Genome Database (web site: http:/
/ Genetic distances between candidate genes and linked markers were obtained from recent publications [Weber et al., 1991; Ben-Othmane et
al., 1992; Bashir et al., 1994; Fougerousse et al., 1994;
Yamaoka et al., 1994; Allamand et al., 1995; PassosBueno et al., 1995b; Lim et al., 1995; Passos-Bueno et
al., 1996]. DNA samples were genotyped according to
protocols reported elsewhere [Sirugo et al., 1992; Rodius et al., 1994] with minor modifications.
Linkage Analysis
Linkage analysis was performed on data obtained
from microsatellite typing of 18 patients, their parents,
and sibs available for study from 4 families using the
LINKAGE programs (versions 5.1 and 5.2) [Lathrop
and Lalouel, 1984] and the FASTLINK version (3.0P)
of the LINKAGE programs [Cottingham et al., 1993;
Schäffer et al., 1994]. MLINK was used for 2-point
Fig. 1. Pedigree of 21 Hutterite patients exhibiting LGMD, 18 of whom participated in the study. The pedigree includes the closest cousin relationships
between the parents of 4 LGMD families (A, B, C, and D) and the parents of patient 5, and at least 1 of the closest links between the families, thus not
all genealogical relationships are shown. Affected individuals are designated with solid symbols, unaffected individuals are designated with open symbols,
and 7 individuals with unknown phenotype are designated with grey symbols. Individuals whose DNA was used for microsatellite genotyping are
indicated with asterisks.
LGMD Does Not Map to Any Known Loci
analysis of an autosomal recessive trait with complete
penetrance. Disease allele frequency was estimated to
be 0.05 based on the number of known cases of LGMD
in Manitoba Hutterites. Marker allele frequencies were
assumed to be equal. No consanguinity or marriage
loops were used.
Pedigree and Clinical Description
Figure 1 shows 21 individuals (13 males and 8 females) who are highly suspected or confirmed to have
LGMD. Disease segregation is compatible with autosomal recessive inheritance. Clinical data from the 18
affected individuals assessed in this study are presented in Table I. Significant intra- and interfamilial
variability is evident. In families A and B, 3 of 14 individuals (patients 4, 9, and 10) have grossly elevated
CK levels (ù15× normal) but are asymptomatic and to
date, their muscle strength is preserved. A dystrophic
muscle biopsy was obtained on patient 4 confirming the
assignment of an affected phenotype. In symptomatic
individuals (patients 1–3, 5–8, 11–18), onset of muscle
weakness and easy fatigability generally were noted
from childhood to mid 30s and clinical progression
tended to be slow. Typically, patients complained of
different degrees of leg weakness and had difficulty
running, climbing stairs, and lifting objects. Six individuals indicated that they suffered neck and back
pain. All symptomatic patients demonstrated slender
proximal and distal muscle mass in their upper and
lower limbs without contractures. There was no evidence of facial muscle weakness in contrast to the reports by Shokeir and Kobrinsky [1976] and Shokeir
and Rozdilsky [1985]. Neither cardiomyopathy nor cardiac conduction defects were present in the patients
included in our study. Ataxia, fasciculations, muscle
cramps, sensory impairment, and myotonia were not
observed. All patients assessed had normal intellect,
bladder, bowel, and swallowing functions, and none
had an associated systemic illness or other disease.
Electromyographic studies have been primarily myopathic with some neurogenic characteristics in several
patients. Muscle biopsies were also compatible with a
dystrophic muscle process. In 1 patient who underwent
a muscle biopsy, grouping of small fibres raised the
possibility of a neurogenic component.
Genealogical Analysis
The ancestry of almost all of the contemporary Hutterites can be traced back to 89 founders (Fujiwara,
Crumley, and Morgan, unpublished data). Thus, the
TABLE I. Clinical Data of Patients With Limb Girdle Muscular Dystrophy
Patient no.
Age at
onset (yr)
Age at
presentation (yr)
mid 20s
mid 20s
Proximal weakness,
fatigue, falling
Muscle wasting &
weakness, back pain
Proximal weakness
Asymptomatic, past
history of carpal
tunnel syndrome
Proximal weakness,
waddling gait
Difficulty climbing
stairs, low back
pain, waddling gait
Weak legs
Neck pain, wasting
of shoulder girdle
Intermittent neck
Proximal weakness,
Proximal weakness
Proximal weakness,
low back pain
Back pain
Proximal weakness
Proximal weakness,
Proximal weakness,
Presenting symptoms
Muscle biopsy
Present status
(age in years)
Ambulatory (37)
Ambulatory (36)
Ambulatory (27)
Asymptomatic (22)
Ambulatory (28)
Ambulatory (26)
Asymptomatic (25)
Asymptomatic (23)
Ambulatory (21)
Ambulatory with
difficulty (36)
Ambulatory (33)
Ambulatory (29)
Ambulatory with
difficulty (45)
Ambulatory with
difficulty (41)
Ambulatory (38)
Wheelchair (60)
Ambulatory (32)
Highest recorded value; normal values for females: 28–116 U/L; normal values for males: 52–175 U/L.
CK reported 4× normal in 1976 [Shokeir and Kobrinsky, 1976].
*Asymptomatic, no data.
Ambulatory (35)
Weiler et al.
contemporary population of >30,000 can be considered
as 1 extended kindred. The Hutterite Brethren established 3 endogamous subdivisions, or leut (Dariusleut,
Lehrerleut, and Schmiedeleut), when they immigrated
to the US in the late 1870s. The Manitoba Hutterites
belong to the Schmiedeleut. We estimated the average
inbreeding coefficient of 10,693 Schmiedeleut considered to be in a 1981 census of our genealogical database
as 0.0338. The kinship coefficient of the parents (or the
inbreeding coefficient of a child) of Families A, B, C,
and D is 0.0172, 0.0651, 0.0452, and 0.0589, respectively. The kinship coefficient is largely due to the closest cousin relationship between the parents, and in
these families is 3rd cousins once-removed in 3 ways,
2nd cousins in 2 ways, 2nd cousins, and half-1st cousins once-removed, respectively (Fig. 1). Patient 5 has 2
affected sibs and is a parent of Family B. The parents
of patient 5 are most closely related as 1st cousins onceremoved and their kinship coefficient is 0.0522. There
are many more distant relationships that also contribute to the kinship coefficient. The total number of ways
the parents are related as cousins is 187, 223, 267, and
154 different ways. The average kinship coefficient of
the 24 pairs of parents who are not married to each
other is 0.0364 (range 4 0.0098 to 0.0880). There are at
least 10 ancestors born in the 1700s who could have
contributed an allele to each of the 8 parents of the
LGMD sibship and to the paternal grandparents of
Family B.
Linkage Analysis
Four families were tested for linkage of the disease
locus to 10 candidate loci on 9 chromosomes. These
include 7 of the currently mapped LGMD loci
(LGMD1A and LGMD2A–LGMD2F) as well as 3 genes
for 4 members of the dystrophin associated protein
complex (DAG1, SNT2B1, and SNT2B2) [IbraghimovBeskrovnaya et al., 1993; Ahn et al., 1996]. Lod scores
ø−2 were obtained for 15 markers (at least 1 marker
linked to each candidate locus) (Table II) suggesting
that each of the 10 candidate loci can be excluded as the
locus causing the disease in these families.
Given the genetic heterogeneity now clearly evident
in LGMD, one strategy is to study large consanguinous
kindreds where the parents of all affected individuals
are likely to carry copies of the same disease allele
identical by descent. The Hutterite families described
in this report represent such a kindred. Genealogical
analysis indicates that the parents of all patients in
this kindred can be traced back to 10 ancestors, 6 to 9
generations back, allowing us to consider the possibility that the disease in each of the patients is caused by
mutation(s) in the same gene.
Physical and laboratory examinations of individuals
from these 4 families have resulted in the identification
of 21 individuals with some or all of the symptoms of
LGMD, 3 of whom did not participate in this study.
Many of our findings on physical examination of symptomatic individuals confirm those of Shokeir and Kobrinsky [1976] and Shokeir and Rozdilsky [1985], including a waddling gait and difficulty in rising from a
squatting position (although we did not see any evidence of the facial muscle involvement that they had
reported). Because of the mild nature of the disease in
this kindred and the overlap between affected and normal individuals with respect to clinical phenotype and
serum CK elevation, we found it difficult to determine
reliably the clinical status of every individual. This is
especially so because serum CK, the most useful biochemical criterion of a muscular dystrophy, is a nonspecific finding and varies in any given individual.
High CK levels may also result, for example, from prolonged or weight-bearing exercise as well as from heatstroke, myocardial infarction, and acute renal failure
[Noakes, 1987]. Phenotypes were therefore defined
stringently to include only those individuals who had
extremely elevated CK levels (ù15× normal), or those
who were symptomatic either with CK ù4× normal or
a positive muscle biopsy. Using these criteria, patients
varied considerably in their clinical phenotype, from
completely asymptomatic to limited ambulation with a
walker. CK levels in our patients were also variable,
from 2× to 25× normal. Seven asymptomatic individu-
TABLE II. Lod Scores From Two-Point Linkage Analysis Between LGMD and Markers Linked to 10 Candidate Loci
Recombination fraction (u)
Markers were chosen on the basis of reported significant positive lod scores to the respective disease loci.
LGMD Does Not Map to Any Known Loci
als with mildly elevated CK were defined as ‘‘unknown’’ to prevent their misclassification.
The variation in phenotype may also be due to differences in the genetic background or the influence of
modifier gene(s). In fact, the involvement of a 2nd locus
in the determination of the clinical phenotype has been
suggested to play a role in 3 of the currently mapped
LGMDs (i.e., LGMD2A, LGMD2B, and LGMD2C)
[Richard et al., 1995; Weiler et al., 1996; McNally et al.,
1996; van Ommen, 1995; Beckmann, 1996]. Phenotypic
variation has also been observed for LGMD2B and
LGMD2C where severe and mild phenotypes are associated with a single haplotype [Weiler et al., 1996] and
a single mutation in g-sarcoglycan, D521-T, respectively [McNally et al., 1996].
Using a conservative definition of the affected phenotype, 2-point linkage analysis of the 12 microsatellite
loci linked to the known LGMD loci (LGMD1A,
LGMD2A–2F) yielded lod scores ø−2 at a recombination fraction of 0.01 and in some cases 0.05 (Table II).
This suggests that the disease in these families does
not map to any of the known LGMD loci. Since most
genes causing LGMD encode members of the dystrophin associated protein complex, we tested markers
linked to 3 genes encoding other members of the complex (DAG1, SNT2B1, and SNT2B2). Two-point linkage analysis of the disease versus these markers has
also yielded lod scores ø−2 which indicates that the
disease in these families does not map to any of these
loci either.
Our study suggests that there is at least 1 more locus
causing autosomal recessive LGMD, in agreement with
the report by Passos-Bueno et al. [1996]. The portion of
the pedigree illustrated here represents only 4 of the
Manitoba families with LGMD in the Schmiedeleut.
We know of 60 Hutterites exhibiting LGMD in Canada
from all 3 subdivisions. The additional families from
the other 2 subdivisions, who are more distantly related to the Manitoba families, will facilitate the mapping of the gene using an identity by descent approach.
This approach was successfully used to map a recessive
gene in the Mennonite population which has a population structure similar to that of the Hutterite population [Puffenberger et al., 1994]. The LGMD disease allele frequency in the Hutterite population appears to
be relatively high since there is no strong clustering
among the 4 Schmiedeleut families and the disease is
present in all 3 subdivisions of the population.
We are indebted to the patients and their families for
their participation in this study. We thank Alejandro
Schäffer for providing the FASTLINK programs, Gail
Coghlan for genealogical information, and the many
referring doctors, consulting neurologists, and the surgeons who performed the muscle biopsies. This work
was supported by the Medical Research Council of
Canada (KW), Muscular Dystrophy Association of
Canada (KW), Manitoba Medical Services Foundation
(KW), Canadian Genetic Diseases Network (KM,
CRG), Winnipeg Rh Institute Foundation (TZ), and the
Children’s Hospital of Winnipeg Research Foundation
(TZ, CRG).
Ahn AH, Freener CA, Gussoni E, Yoshida M, Ozawa E, Kunkel LM (1996):
The three human syntrophin genes are expressed in diverse tissues,
have distinct chromosomal locations, and each bind to dystrophin and
its relatives. J Biol Chem 271:2724–2730.
Allamand V, Broux O, Richard I, Fougerousse F, Chiannilkulchai N, Bourg
N, Brenguier L, Devaud C, Pasturaud P, Pereira de Souza A, Roudaut
C, Tischfield JA, Conneally PM, Fardeau M, Cohen D, Jackson CE,
Beckmann JS (1995): Preferential localization of the limb-girdle muscular dystrophy type 2A gene in the proximal part of a 1-cM 15q15.1q15.3 interval. Am J Hum Genet 56:1417–1430.
Bashir R, Strachan T, Keers S, Stephenson A, Mahjneh I, Marconi G,
Nashef L, Bushby KM (1994): A gene for autosomal recessive limbgirdle muscular dystrophy maps to chromosome 2p. Hum Mol Genet
Beckmann JS (1996): The Reunion paradox and the digenic model. Am J
Hum Genet 59:1400–1402.
Bejaoui K, Hirabayashi K, Hentati F, Haines JL, Ben-Hamida C, Belal S,
Miller RG, McKenna-Yasek D, Weissenbach J, Rowland LP, Griggs RC,
Munsat TL, Ben Hamida M, Arahata K, Brown RH Jr. (1995): Linkage
of Miyoshi myopathy (distal autosomal recessive muscular dystrophy)
locus to chromosome 2p12-14. Neurology 45:768-772.
Ben Othmane K, Speer MC, Stauffer J, Blel S, Middleton L, Ben Hamida
C, Etribi A, Loeb D, Hentati F, Roses AD, Ben Hamida M, PericakVance MA, Vance JM (1995): Evidence for linkage disequilibrium in
chromosome 13-linked Duchenne-like muscular dystrophy (LGMD2C).
Am J Hum Genet 57:732–734.
Ben-Othmane K, Ben-Hamida M, Pericak-Vance MA, Ben-Hamida C, Blel
S, Carter SC, Bowcock AM, Petruhkin K, Gilliam TC, Roses AD, Hentati F, Vance JM (1992): Linkage of Tunisian autosomal recessive Duchenne-like muscular dystrophy to the pericentromeric region of chromosome 13q. Nat Genet 2:315–317.
Bönnemann CG, Modi R, Noguchi S, Mizuno Y, Yoshida M, Gussoni E,
McNally EM, Duggan DJ, Angelini C, Hoffman EP, Ozawa E, Kunkel
LM (1995): b-sarcoglycan (A3b) mutations cause autosomal recessive
muscular dystrophy with loss of the sarcoglycan complex. Nat Genet
Cottingham Jr. RW, Idury RM, Schäffer AA (1993): Faster sequential genetic linkage computations. Am J Hum Genet 53:252–263.
Fougerousse F, Broux O, Richard I, Allamand V, Pereira de Souza A, Bourg
N, Brenguier L, Devaud C, Pasturaud P, Roudaut C, Chiannilkulchai
N, Hillaire D, Bui H, Chumakov I, Weissenbach J, Cherif D, Cohen D,
Beckmann J (1994): Mapping of a chromosome 15 region involved in
limb girdle muscular dystrophy. Hum Mol Genet 3:285–293.
Greenberg CR, Hamerton JL, Nigli M, Wrogemann K (1987): DNA studies
in a family with Duchenne muscular dystrophy and a deletion at Xp21.
Am J Hum Genet 41:128–137.
Gross D (1996): ‘‘Schmiedeleut Family Record.’’ High Bluff, Manitoba,
Canada: Sommerfeld Printshop.
Ibraghimov-Beskrovnaya O, Milatovich A, Ozcelik T, Yang B, Koepnick K,
Francke U, Campbell KP (1993): Human dystroglycan: Skeletal muscle
cDNA, genomic structure, origin of tissue specific isoforms and chromosomal localization. Hum Mol Genet 2:1651–1657.
Lathrop GM, Lalouel JM (1984): Easy calculations of lod scores and genetic
risks on small computers. Am J Hum Genet 36:460–465.
Lim LE, Duclos F, Broux O, Bourg N, Sunada Y, Allamand V, Meyer J,
Richard I, Moomaw C, Slaughter C, Tomé FMS, Fardeau M, Jackson
CE, Beckmann JS, Campbell KP (1995): b-sarcoglycan: Characterization and role in limb-girdle muscular dystrophy linked to 4q12. Nat
Genet 11:257–265.
McNally EM, Passos-Bueno MR, Bonnemann CG, Vainzof M, de Sà
Moreira E, Lidov HG, Ben Othmane K, Denton PH, Vance JM, Zatz M,
Kunkel LM (1996): Mild and severe muscular dystrophy caused by a
single gamma-sarcoglycan mutation. Am J Hum Genet 59:1040–1047.
Nigro V, Piluso G, Belsito A, Politano L, Puca AA, Papparella S, Rossi E,
Viglietto G, Esposito MG, Abbondanza C, Medici N, Molinari AM, Nigro G, Puca GA (1996): Identification of a novel sarcoglycan gene at
5q33 encoding a sarcolemmal 35 kDa glycoprotein. Hum Mol Genet
Noakes TD (1987): Effect of exercise on serum activities in humans. Sports
Med 4:245–267.
Noguchi S, McNally EM, Ben Othmane K, Hagiwara Y, Mizuno Y, Yoshida
M, Yamamoto H, Bönnemann CG, Gussoni E, Denton PH, Kyriakides
T, Middleton L, Hentati F, Ben Hamida M, Nonaka I, Vance JM,
Weiler et al.
Kunkel LM, Ozawa E (1995): Mutations in the dystrophin-associated
protein G-sarcoglycan in chromosome 13 muscular dystrophy. Science
Passos-Bueno MR, Bashir R, Moreira ES, Vainzof M, Marie SK, Vasquez L,
Iughetti P, Bakker E, Keers S, Stephenson A, Strachan T, Mahneh I,
Weissenbach J, Bushby K, Zatz M (1995a): Confirmation of the 2p locus
for the mild autosomal recessive limb-girdle muscular dystrophy gene
(LGMD2B) in three families allows refinement of the candidate region.
Genomics 27:192–195.
Passos-Bueno MR, Moreira ES, Vainzof M, Chamberlain J, Marie SK,
Pereira L, Akiyama J, Roberds SL, Campbell KP, Zatz M (1995b): A
common missense mutation in the adhalin gene in three unrelated
Brazilian families with a relatively mild form of autosomal recessive
limb-girdle muscular dystrophy. Hum Mol Genet 4:1163–1167.
Passos-Bueno MR, Moreira ES, Vainzof M, Marie SK, Zatz M (1996): Linkage analysis in autosomal recessive limb-girdle muscular dystrophy
(AR LGMD) maps a sixth form to 5q33-34 (LGMD2F) and indicates
that there is at least 1 more subtype of AR LGMD. Hum Mol Genet
Puffenberger EG, Kauffman ER, Bolk S, Matise TC, Washington SS, Angrist M, Weissenbach J, Garver KL, Mascari M, Ladda R, Slaugenhaupt SA, Chakravarti A (1994): Identity-by-descent and association
mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. Hum Mol Genet 3:1217–1225.
Richard I, Broux O, Allamand V, Fougerousse F, Chiannilkulchai N, Bourg
N, Brenguier L, Devaud C, Pasturaud P, Roudaut C, Hillaire D, PassosBueno MR, Zatz M, Tischfield JA, Fardeau M, Jackson CE, Cohen D,
Beckmann JS (1995): Mutations in the proteolytic enzyme calpain 3
cause limb-girdle muscular dystrophy type 2A. Cell 81:27–40.
Roberds SL, Leturcq F, Allamand V, Piccolo F, Jeanpierre M, Anderson
RD, Lim LE, Lee JC, Tomé FM, Romero NB, Fardeau M, Beckmann JS,
Kaplan J-C, Campbell KP (1994): Missense mutations in the adhalin
gene linked to autosomal recessive muscular dystrophy. Cell 78:625–
Rodius F, Duclos F, Wrogemann K, LePaslier D, Ougen P, Billault P, Belal
S, Musenger C, Brice A, Dürr A, Mignard C, Sirugo G, Weissenbach J,
Cohen D, Hentati F, Ben Hamida M, Mandel JL, Koenig M (1994):
Recombinations in individuals homozygous by descent localise the
Friedreich ataxia locus in a cloned 450 kb interval. Am J Hum Genet
Schäffer AA, Gupta SK, Shriram K, Cottingham Jr RW (1994): Avoiding
recomputation in linkage analysis. Hum Hered 44:225–237.
Shokeir MHK, Kobrinsky NL (1976): Autosomal recessive muscular dystrophy in Manitoba Hutterites. Clin Genet 9:197–202.
Shokeir MHK, Rozdilsky B (1985): Muscular dystrophy in Saskatchewan
Hutterites. Am J Med Genet 22:487–493.
Sirugo G, Keats B, Fujita R, Duclos F, Purohit K, Koenig M, Mandel JL
(1992): Friedreich ataxia locus in Louisiana Acadians: Demonstration
of a founder effect by analysis of microsatellite-generated extended
haplotypes. Hum Genet 50: 559–566.
Speer MC, Yamaoka LH, Gilchrist JH, Gaskell CP, Stajich JM, Vance JM,
Kazantsev A, Lastra AA, Haynes CS, Beckmann JS, Cohen D, Weber
JL, Roses AD, Pericak-Vance MA (1992): Confirmation of genetic heterogeneity in limb-girdle muscular dystrophy: Linkage of an autosomal
dominant form to chromosome 5q. Am J Hum Genet 50:1211–1217.
Van der Kooi AJ, van Meegen M, Ledderhof TM, McNally EM, de Visser M,
Bolhuis PA (1997): Genetic localization of a newly recognized autosomal dominant limb-girdle muscular dystrophy with cardiac involvement (LGMD1B) to chromosome 1q11-21. Am J Hum Genet 60:891–
van Ommen G-J (1995): A foundation for limb-girdle muscular dystrophy.
Nature Med 1:412–414.
Weber JL, Polymeropoulos MH, May PE, Kwitek AE, Xiao H, McPherson
JD, Wasmuth JJ (1991): Mapping of human chromosome 5 microsatellite DNA polymorphisms. Genomics 11:695–700.
Weiler T, Greenberg CR, Nylen E, Halliday W, Morgan K, Eggertson D,
Wrogemann K (1996): Limb-girdle muscular dystrophy and Miyoshi
myopathy in an aboriginal Canadian kindred map to LGMD2B and
segregate with the same haplotype. Am J Hum Genet 59:872–878.
Yamaoka LH, Westbrook CA, Speer MC, Gilchrist JM, Jabs EW, Schweins
EG, Stajich JM, Gaskell PC, Roses AD, Pericak-Vance MA (1994): Development of a microsatellite genetic map spanning 5q31-q33 and subsequent placement of the LGMD1A locus between D5S178 and IL9.
Neuromusc Disord 4:471–475.
Без категории
Размер файла
154 Кб
Пожаловаться на содержимое документа