A new form of autosomal dominant limb-girdle muscular dystrophy (LGMD1G) with progressive fingers and toes flexion limitation maps to chromosome 4p21

Abstract

Limb-girdle muscular dystrophy (LGMD) is a genetic disorder characterized by progressive weakness of pelvic and scapular girdles and great clinical variability. It is a highly heterogeneous disease with 16 identified loci: six of them autosomal dominant (AD) (LGMD1) and 10 autosomal recessive (AR) (LGMD2). The responsible genes are known for three of the AD-LGMD and for all 10 AR-LGMD. Linkage analysis excluded these 16 loci in a Brazilian-Caucasian family with 12 patients affected by AD late-onset LGMD associated with progressive fingers and toes flexion limitation. Biceps muscle biopsy from one of the patients showed a predominantly myopathic histopathological pattern, associated with rimmed vacuoles. A genomewide scan was performed which mapped a new locus for this disorder at 4p21 with a maximum two-point lod score of 6.62 for marker D4S2964. Flanking markers place this locus between D4S2947 and D4S2409, within an interval of 9 cM. We propose to classify this AD form of LGMD as LGMD1G.

Late-onset autosomal dominant limb girdle muscular dystrophy and Paget's disease of bone unlinked to the VCP gene locus

“…These are originally defined by proximal muscle weakness and dystrophic findings on a skeletal muscle biopsy. Underlying genetic defects have been identified for subtypes LGMD1A-C and only the genetic locus is known for the remaining LGMD1E-G [3][4][5]. A further small group of adult-onset autosomal dominant muscular dystrophies is characterized by additional extramuscular findings, pathohistological distinctive features or genetic mutations.…”

Clinical, molecular, and protein correlations in a large sample of genetically diagnosed Italian limb girdle muscular dystrophy patients

“…There are at least 19 different subtypes of LGMD, seven with an autosomal dominant and 12 with an autosomal recessive pattern of inheritance [Bushby, 1999;Mathews and Moore, 2003;Starling et al, 2004;Guglieri et al, 2005;D'Amico et al, 2006;Jarry et al, 2007;Moore et al, 2006]. The autosomal dominant forms (LGMD1) are relatively rare and represent probably less than 10% of all LGMD cases.…”

Diagnosis of the Muscular Dystrophies

“…A second form of myotonic dystrophy (DM2) is due to mutations in the ZNF9 gene, does not have a congenital onset form, and is probably less common. FSHD is characterised by weakness of the facial, scapular, ankle and upper arm muscles and is caused by deletions of large D4Z4 DNA repeats in the sub-telomeric region of chromosome 4q (McNally and Pytel 2007;Pandya, King et al 2008 (Wijmenga, Frants et al 1990), 2 (Brook, McCurrach et al 1992), 3 (Renwick, Bundey et al 1971), 4 (Liquori, Ricker et al 2001), 5 (Ranum, Rasmussen et al 1998), 6(Brais, Bouchard et al 1998, 7 (Brais, Xie et al 1995), 8(Robinson, Hammans et al 2005, 9 (Hayashi, Matsuda et al 2009), 10(Burghes, Logan et al 1987, 11 (Hoffman, Brown et al 1987), 12 (Koenig, Hoffman et al 1987), 13 (Koenig, Monaco et al 1988), 14 (Monaco, Neve et al 1986), 15 (Bione, Maestrini et al 1994), 16 (Gueneau, Bertrand et al 2009), 17 (Bonne, Di Barletta et al 1999), 18 (Zhang, Bethmann et al 2007), 19 (Hauser, Horrigan et al 2000), 20 (Muchir, Bonne et al 2000), 21 (McNally, de Sa Moreira et al 1998), 22 (Minetti, Sotgia et al 1998), 23 (Speer, Vance et al 1999), 24 (Messina, Speer et al 1997), 25 (Palenzuela, Andreu et al 2003), 26 (Starling, Kok et al 2004), 27 (Richard, Brenguier et al 1997), 28 (Richard, Broux et al 1995), 29 (Bashir, Britton et al 1998), 30 (Liu, Aoki et al 1998), 31 (Noguchi, McNally et al 1995), 32 (Roberds, Leturcq et al 1994), 33 …”