Autosomal dominant Brody disease cosegregates with a chromosomal (2;7)(p11.2;p12.1) translocation in an Italian family

Abstract

Brody disease is a rare muscle disorder characterized by exercise-induced impairment in muscle relaxation, due to a markedly reduced influx of calcium ions in the sarcoplasmic reticulum. A subset of autosomal recessive families harbour mutations in the ATP2A1 gene, encoding the fast-twitch skeletal muscle sarcoplasmic reticulum Ca 2 þ ATPase (SERCA1). Rare autosomal dominant families have been described, in which ATP2A1 was excluded as the causative gene, further supporting genetic heterogeneity. We report four individuals from a three-generation Italian family with a clinical phenotype of Brody disease, in which linkage analysis excluded ATP2A1 as the responsible gene. The disease cosegregates in an autosomal dominant fashion with an apparently balanced constitutional chromosome translocation (2;7)(p11.2;p12.1), suggesting a causal relationship between the rearrangement and the phenotype. FISH analysis using YAC and PAC clones as probes refined the breakpoint regions to genomic segments of about 164 and 120 kb, respectively, providing a possible clue to pinpoint the location of a novel gene responsible for this rare muscle disorder.

accordion, a zebrafish behavioral mutant, has a muscle relaxation defect due to a mutation in the ATPase Ca2+ pump SERCA1

“…Most families harboring Brody disease show an autosomal recessive inheritance pattern and carry a mutation in the ATP2A1 gene on chromosome 16 (Odermatt et al, 1996;Odermatt et al, 1997;Odermatt et al, 2000). In a minority of cases, Brody disease is inherited in an autosomal recessive pattern but there are no mutations in ATP2A1 (MacLennan, 2000;Zhang et al, 1995) or in an autosomal dominant pattern with a (2;7) chromosomal translocation (Novelli et al, 2004). Thus, there are at least two genes other than ATP2A1 that can give rise to Brody disease (MacLennan, 2000).…”

Brody syndrome: A clinically heterogeneous entity distinct from Brody disease

“…This patient had previously been reported to have exertional rhabdomyolysis [21]. CK increase with a history of rhabdomyolysis and myoglobinuria has been reported in only one other Brody syndrome patient (L29) [13]. In all other patients, CK was normal.…”

“…We reviewed all publications cited by Pubmed on 'Brody disease', 'Brody syndrome' or 'Brody myopathy' since the initial description in 1969 by Brody [2] until 2010 and the references of these articles, and selected all patients in whom clinical data were available (n = 32; Supplementary Table 1) [2,4,5,[7][8][9][10][11][12][13][14]. We classified them as literature ("L") cases, numbered them chronologically, and screened the case descriptions for clinical key features of Brody disease.…”

“…Since the initial report of Brody in 1969 until 2010, 35 patients have been reported in the literature, of which 32 with a description of clinical features (L1-L32 in Tables 2A, 2B and Supplementary Table 1) [3][4][5][7][8][9][10][12][13][14][20][21][22][23]. L1 represents the patient reported by Brody in 1961 [2].…”

Transfection efficiency in rat soleus and SERCA1b expression in human skeletal muscles

“…Clinical data have been previously reported [14]. Briefly, this 38-year-old man was referred for muscle rigidity with neonatal onset.…”