Linkage of Tunisian autosomal recessive Duchenne–like muscular dystrophy to the pericentromeric region of chromosome 13q

Othmane, Kamel Ben; Hamida, M. Ben; Pericak‐Vance, Margaret A.; Hamida, Christiane Ben; S, Blel; Carter, Susan C.; Bowcock, Anne M.; Petruhkin, Konstantin; Gilliam, T. Conrad; Roses, Allen D.; Hentati, Fayçal; Vance, Jeffery M.

doi:10.1038/ng1292-315

Cited by 158 publications

(50 citation statements)

References 17 publications

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“…LGMD2A (CAPN3 at 15q15.1), 2,3 LGMD2B (DYSF at 2p12 -16), 4,5 LGMD2C (SGCG at 13q12), 6,7 LGMD2D (ADL at 17q12 -q21.33), 8 -10 LGMD2E (SGCB at 4q12), 11,12 LGMD2F (SGCD at 5q33 -34), 13,14 LGMD2G (TCAP at 17q11 -q12), 1,15 LGMD2H (TRIM32 at 9q31 -q34.1), 16,17 LGMD2I (FKRP at 19q13.3), 18,19 and LGMD2J (TTN at 2q31). 20 The involved genes encode either structural components of muscle, that is, g-, a-, b-, and d-sarcoglycans, responsible for LGMD2C to 2F, respectively, or proteins of other functions.…”

Section: Introductionmentioning

confidence: 99%

Limb-girdle muscular dystrophy 2I: phenotypic variability within a large consanguineous Bedouin family associated with a novel FKRP mutation

et al. 2003

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Limb-girdle muscular dystrophies (LGMDs) represent a group of diseases characterized mainly by muscle wasting of the upper and lower limbs, with a wide range of clinical severity. The clinical heterogeneity is paralleled by molecular heterogeneity; each of the 10 forms of autosomal-recessive LGMD recognized to date is caused by mutations in a distinct gene. In a large consanguineous Bedouin tribe living in northern Israel, 15 individuals affected by LGMD demonstrate an autosomal recessive pattern of inheritance. A genome-wide screen followed by fine mapping in this family revealed linkage to a region on chromosome 19 harboring the fukutin-related protein gene (FKRP), with a maximal LOD score of 4.8 for D19S902. FKRP, encoding a putative glycosyltransferase, has been implicated in causing congenital muscular dystrophy 1C (MDC1C), and has recently been shown to be mutated in LGMD2I. We identified a novel missense mutation in exon 4 of the FKRP gene in all the patients studied. Although all affected individuals were homozygous for the same mutation, a marked phenotypic variability was apparent within the family. This finding may suggest a role of modifier genes and environmental factors in LGMD2I. Moreover, the demonstration that an identical, novel mutation in the FKRP gene can cause a muscle disease of either a congenital onset or of a later onset within a single family provides clinical support to the molecular evidence, suggesting that MDC1C and LGMD2I are overlapping ends of one and the same entity.

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Section: Introductionmentioning

confidence: 99%

Limb-girdle muscular dystrophy 2I: phenotypic variability within a large consanguineous Bedouin family associated with a novel FKRP mutation

et al. 2003

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“…The linkage of SCARMD with chromosome 13 has been observed in several North African families who demonstrate a loss of anti-adhalin immunoreactivity on muscle biopsies (22). The mapping of human adhalin to chromosome 17 excludes the adhalin gene as the locus for this disorder.…”

Section: Discussionmentioning

confidence: 99%

“…In the North African population, it constitutes a significant percentage of patients with muscular dystrophy. Linkage of the chromosome 13 markers D13S115 and D13S143 with the SCARMD phenotype has been demonstrated in several Tunisian families (Z = 9.15 and Z = 8.36, respectively) (22). Several Brazilian families with a Duchenne-like autosomal dystrophy have not shown linkage to chromosome 13 but do show an absence of anti-adhalin staining on muscle biopsies (23).…”

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confidence: 99%

Human adhalin is alternatively spliced and the gene is located on chromosome 17q21.

McNally

Yoshida

Mizuno

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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Mutations in the dystrophin gene cause the X chromosome-linked, recessive Duchenne and Becker muscular dystrophies. Dystrophin, a large cytoskeletal protein, copurifles with a complex of dystrophin-aclated proteins which serve to anchor dystrophin to the sarcolemma. One of these associated proteins, adhalin, has been implicated as a candidate for severe childhood autosomal recessive muscular dystrophy (SCARMD) due to absence of anti-adhalin sning in muscle biopsy samples taken from SCARMD patients. Furthermore, the Duchenne-like dystrophic phenotype seen in the SCARMD families was shown to be tightly linked to chromosome 13 markers. To determine the genetic mutation responsible for autosomal dystrophy, we characterized the human adhalin gene. Contrary to our expectation, human adhalin was mapped to chromosome 17q21, excluding adhalin as the gene causing chromosome 13-associated SCARMD. Additionaily, a splice form of adhalin message was found that predicts a 35-kDa nontransmembrane adhalin. The expression of both adhalin splice forms is exclusively restricted to striated muscle, unlike other components of the dystrophin-glycoprotein complex.Genetic analyses of patients with Duchenne and Becker muscular dystrophy (DMD/BMD) have demonstrated a correlation between mutations in dystrophin's carboxyl terminus and a more severe clinical course (1). The carboxyl terminus of dystrophin binds a complex of dystrophinassociated proteins (DAPs), and components of this glycoprotein complex are decreased in DMD (2-5). Several DAPs have been identified by virtue of their copurification with dystrophin (6-8). These include the 156-and 43-kDa glycoproteins, together named dystroglycan, that are produced from one transcript encoded by a single gene on chromosome 3p21 (9,10). Three separate genes encode the 59-kDa nonglycosylated members of the complex, called syntrophins (11,12). Three additional proteins (50, 35, and 25 kDa) also participate in dystrophin's membrane interaction (6-8, 13). Using partial peptide sequences generated from proteolytic digestion of the rabbit 50-kDa DAP, Roberds et al. (13) identified a cDNA encoding the rabbit 50-kDa DAP and termed it adhalin. Isoelectric focusing analysis of the smaller components of the glycoprotein complex has suggested that the 35-kDa DAP may be heterogeneous (8).Dystroglycan and the syntrophins are expressed in tissues that lack the full-length dystrophin (10)(11)(12). This has raised speculation that in vivo, dystroglycan and the syntrophins may interact with proteins other than dystrophin. In vitro, syntrophin binds the carboxyl terminus of dystrophin, and dystroglycan has been shown to bind the extracellular matrix component laminin in a gel overlay assay (9,(14)(15)(16) gene (20, 24).In an effort to understand the genetic mutation responsible for SCARMD, we isolated and characterized cDNA and genomic sequences encoding human adhalin. To our surprise, the adhalin gene resides on chromosome 17q21, unlinked to the chromosome 13-encoded SCARMD locus. Additionally, a spli...

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“…These criteria have allowed distinction between SCARMD and DMD. SCARMD was first linked to the pericentromeric region of chromosome 13q12 in several North African families [23][24][25] and excluded from the 13q locus in non-North African families [26,27]. Therefore, mutations in at least two independent genes may cause SCARMD.…”

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confidence: 99%

Absence of γ‐sarcoglycan (35 DAG) in autosomal recessive muscular dystrophy linked to chromosome 13q12

et al. 1996

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We have partially sequenced rabbit skeletal muscle T-sarcoglycan an integral component of the dystrophin-glycoprotein complex. Specific antibodies were produced against a 7-sarcoglycan peptide and used to examine the expression of T-sarcoglycan in skeletal muscle of patients with severe childhood autosomal muscular dystrophy linked to chromosome 13q12 (SCARMD). We show by immunofluorescence and Western blotting that in skeletal muscle from these patients T-sarcoglycan is completely absent and c~-and ~-sarcoglycan are greatly reduced in abundance, whereas other components of the DGC are preserved. In addition, we show that in normal muscle ~-, ~-, and T-sarcoglycan constitute a tightly associated sarcolemma complex which can not be disrupted by SDS treatment.

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Linkage of Tunisian autosomal recessive Duchenne–like muscular dystrophy to the pericentromeric region of chromosome 13q

Cited by 158 publications

References 17 publications

Limb-girdle muscular dystrophy 2I: phenotypic variability within a large consanguineous Bedouin family associated with a novel FKRP mutation

Limb-girdle muscular dystrophy 2I: phenotypic variability within a large consanguineous Bedouin family associated with a novel FKRP mutation

Human adhalin is alternatively spliced and the gene is located on chromosome 17q21.

Absence of γ‐sarcoglycan (35 DAG) in autosomal recessive muscular dystrophy linked to chromosome 13q12

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