Next generation sequencing on patients with LGMD and nonspecific myopathies: Findings associated with ANO5 mutations

Savarese, Marco; Fruscio, Giuseppina Di; Tasca, Giorgio; Ruggiero, Lucia; Janssens, Sandra; Bleecker, Jan De; Delpech, Marc; Musumeci, Olimpia; Toscano, Antonio; Angelini, C.; Sacconi, Sabrina; Santoro, Lucio; Ricci, Enzo; Claes, Kathleen; Politano, Luisa; Nigro, Vincenzo

doi:10.1016/j.nmd.2015.03.011

Cited by 64 publications

(81 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TMEM16E loss-of-function mutations cause muscular dystrophy in humans (12) (Fig. 9C) and sperm motility defects in mice (this report), while autosomal dominant mutations cause GDD (11).…”

Section: Discussionmentioning

confidence: 52%

“…Since TMEM16A, the first-identified TMEM16 family protein, functions as a Ca 2ϩ -dependent Cl Ϫ channel (14)(15)(16), TMEM16E was also thought to be a Cl Ϫ channel (12). We demonstrated that TMEM16F supports Ca 2ϩ -dependent phospholipid scrambling at plasma membranes (6,17), and TMEM16F's ability to scramble phospholipids was recently confirmed by two other groups (18,19).…”

mentioning

confidence: 54%

“…4C). Although human patients carrying TMEM16E mutations suffer from muscular dystrophy (8,12), the skeletal muscles in the TMEM16E Ϫ/Ϫ mice, regardless of age or sex, had no apparent abnormalities (Fig. 4D and data not shown).…”

Section: Tmem16e Cellular Localizationmentioning

confidence: 91%

“…Subsequently, TMEM16E homozygous and compound heterozygous mutations (missense or frameshift mutations) and a dominant missense mutation were found in patients with autosomal muscular dystrophies (8)(9)(10) and GDD (11). A recent cohort analysis of 786 patients with autosomal recessive limb-girdle muscular dystrophies (LGMD) and generic myopathy found that about 4% and 3% of the patients, respectively, carried pathological homozygous or compound heterozygous TMEM16E mutations (12).…”

mentioning

confidence: 99%

See 3 more Smart Citations

A Role of TMEM16E Carrying a Scrambling Domain in Sperm Motility

Gyobu

Miyata

Ikawa

et al. 2016

Molecular and Cellular Biology

View full text Add to dashboard Cite

cTransmembrane protein 16E (TMEM16E) belongs to the TMEM16 family of proteins that have 10 transmembrane regions and appears to localize intracellularly. Although TMEM16E mutations cause bone fragility and muscular dystrophy in humans, its biochemical function is unknown. In the TMEM16 family, TMEM16A and -16B serve as Ca 2؉ -dependent Cl ؊ channels, while TMEM16C, -16D, -16F, -16G, and -16J support Ca 2؉ -dependent phospholipid scrambling. Here, we show that TMEM16E carries a segment composed of 35 amino acids homologous to the scrambling domain in TMEM16F. When the corresponding segment of TMEM16A was replaced by this 35-amino-acid segment of TMEM16E, the chimeric molecule localized to the plasma membrane and supported Ca 2؉ -dependent scrambling. We next established TMEM16E-deficient mice, which appeared to have normal skeletal muscle. However, fertility was decreased in the males. We found that TMEM16E was expressed in germ cells in early spermatogenesis and thereafter and localized to sperm tail. TMEM16E ؊/؊ sperm showed no apparent defect in morphology, beating, mitochondrial function, capacitation, or binding to zona pellucida. However, they showed reduced motility and inefficient fertilization of cumulus-free but zona-intact eggs in vitro. Our results suggest that TMEM16E may function as a phospholipid scramblase at inner membranes and that its defect affects sperm motility.

show abstract

“…TMEM16E loss-of-function mutations cause muscular dystrophy in humans (12) (Fig. 9C) and sperm motility defects in mice (this report), while autosomal dominant mutations cause GDD (11).…”

Section: Discussionmentioning

confidence: 52%

mentioning

confidence: 54%

Section: Tmem16e Cellular Localizationmentioning

confidence: 91%

mentioning

confidence: 99%

See 2 more Smart Citations

A Role of TMEM16E Carrying a Scrambling Domain in Sperm Motility

Gyobu

Miyata

Ikawa

et al. 2016

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…and Savarese et al 130 for TMEM16E, from Suzuki et al 40 and Castoldi et al 93 for TMEM16F, and Vermeer et al 131 and Balreira et al 132 for TMEM16K Figure 3 The molecular mechanism for PtdSer exposure in cells with high Ca 2+ -concentration. The flippase comprised of P4-ATPase (ATP11A or ATP11C) and CDC50A, and a Ca 2+ -dependent scramblase (TMEM16F) are schematically shown.…”

mentioning

confidence: 99%

Exposure of phosphatidylserine on the cell surface

et al. 2016

View full text Add to dashboard Cite

Clinical and molecular findings in a cohort of ANO5‐related myopathy

Silva

Coimbra-Neto

Souza

et al. 2019

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective ANO5‐related myopathy is an important cause of limb‐girdle muscular dystrophy (LGMD) and hyperCKemia. The main descriptions have emerged from European cohorts, and the burden of the disease worldwide is unclear. We provide a detailed characterization of a large Brazilian cohort of ANO5 patients. Methods A national cross‐sectional study was conducted to describe clinical, histopathological, radiological, and molecular features of patients carrying recessive variants in ANO5. Correlation of clinical and genetic characteristics with different phenotypes was studied. Results Thirty‐seven patients from 34 nonrelated families with recessive mutations of ANO5 were identified. The most common phenotype was LGMD, observed in 25 (67.5%) patients, followed by pseudometabolic presentation in 7 (18.9%) patients, isolated asymptomatic hyperCKemia in 4 (10.8%) patients, and distal myopathy in a single patient. Nine patients presented axial involvement, including one patient with isolated axial weakness. The most affected muscles according to MRI were the semimembranosus and gastrocnemius, but paraspinal and abdominal muscles, when studied, were involved in most patients. Fourteen variants in ANO5 were identified, and the c.191dupA was present in 19 (56%) families. Sex, years of disease, and the presence of loss‐of‐function variants were not associated with specific phenotypes. Interpretation We present the largest series of anoctaminopathy outside Europe. The most common European founder mutation c.191dupA was very frequent in our population. Gender, disease duration, and genotype did not determine the phenotype.

show abstract

Next generation sequencing on patients with LGMD and nonspecific myopathies: Findings associated with ANO5 mutations

Cited by 64 publications

References 31 publications

A Role of TMEM16E Carrying a Scrambling Domain in Sperm Motility

A Role of TMEM16E Carrying a Scrambling Domain in Sperm Motility

Exposure of phosphatidylserine on the cell surface

Clinical and molecular findings in a cohort of ANO5‐related myopathy

Contact Info

Product

Resources

About