Angela Loi

@article{marongiu_novel_2016,

title = {Novel action of FOXL2 as mediator of Col1a2 gene autoregulation},

author = {Mara Marongiu and Manila Deiana and Loredana Marcia and Andrea Sbardellati and Isadora Asunis and Alessandra Meloni and Andrea Angius and Roberto Cusano and Angela Loi and Francesca Crobu and Giorgio Fotia and Francesco Cucca and David Schlessinger and Laura Crisponi},

doi = {10.1016/j.ydbio.2016.05.022},

issn = {1095-564X},

year  = {2016},

date = {2016-08-01},

journal = {Developmental Biology},

volume = {416},

number = {1},

pages = {200--211},

abstract = {FOXL2 belongs to the evolutionarily conserved forkhead box (FOX) superfamily and is a master transcription factor in a spectrum of developmental pathways, including ovarian and eyelid development and bone, cartilage and uterine maturation. To analyse its action, we searched for proteins that interact with FOXL2. We found that FOXL2 interacts with specific C-terminal propeptides of several fibrillary collagens. Because these propeptides can participate in feedback regulation of collagen biosynthesis, we inferred that FOXL2 could thereby affect the transcription of the cognate collagen genes. Focusing on COL1A2, we found that FOXL2 indeed affects collagen synthesis, by binding to a DNA response element located about 65Kb upstream of this gene. According to our hypothesis we found that in Foxl2(-/-) mouse ovaries, Col1a2 was elevated from birth to adulthood. The extracellular matrix (ECM) compartmentalizes the ovary during folliculogenesis, (with type I, type III and type IV collagens as primary components), and ECM composition changes during the reproductive lifespan. In Foxl2(-/-) mouse ovaries, in addition to up-regulation of Col1a2, Col3a1, Col4a1 and fibronectin were also upregulated, while laminin expression was reduced. Thus, by regulating levels of extracellular matrix components, FOXL2 may contribute to both ovarian histogenesis and the fibrosis attendant on depletion of the follicle reserve during reproductive aging and menopause.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{angius_bi-allelic_2016,

title = {Bi-allelic Mutations in KLHL7 Cause a Crisponi/CISS1-like Phenotype Associated with Early-Onset Retinitis Pigmentosa},

author = {Andrea Angius and Paolo Uva and Insa Buers and Manuela Oppo and Alessandro Puddu and Stefano Onano and Ivana Persico and Angela Loi and Loredana Marcia and Wolfgang H{ö}hne and Gianmauro Cuccuru and Giorgio Fotia and Manila Deiana and Mara Marongiu and Hatice Tuba Atalay and Sibel Inan and Osama {El Assy} and Leo M E Smit and Ilyas Okur and Koray Boduroglu and G{ü}len Eda Utine and Esra Kılı{ç} and Giuseppe Zampino and Giangiorgio Crisponi and Laura Crisponi and Frank Rutsch},

doi = {10.1016/j.ajhg.2016.05.026},

issn = {1537-6605},

year  = {2016},

date = {2016-07-01},

journal = {American Journal of Human Genetics},

volume = {99},

number = {1},

pages = {236--245},

abstract = {Crisponi syndrome (CS)/cold-induced sweating syndrome type 1 (CISS1) is a very rare autosomal-recessive disorder characterized by a complex phenotype with high neonatal lethality, associated with the following main clinical features: hyperthermia and feeding difficulties in the neonatal period, scoliosis, and paradoxical sweating induced by cold since early childhood. CS/CISS1 can be caused by mutations in cytokine receptor-like factor 1 (CRLF1). However, the physiopathological role of CRLF1 is still poorly understood. A subset of CS/CISS1 cases remain yet genetically unexplained after CRLF1 sequencing. In five of them, exome sequencing and targeted Sanger sequencing identified four homozygous disease-causing mutations in kelch-like family member 7 (KLHL7), affecting the Kelch domains of the protein. KLHL7 encodes a BTB-Kelch-related protein involved in the ubiquitination of target proteins for proteasome-mediated degradation. Mono-allelic substitutions in other domains of KLHL7 have been reported in three families affected by a late-onset form of autosomal-dominant retinitis pigmentosa. Retinitis pigmentosa was also present in two surviving children reported here carrying bi-allelic KLHL7 mutations. KLHL7 mutations are thus associated with a more severe phenotype in recessive than in dominant cases. Although these data further support the pathogenic role of KLHL7 mutations in a CS/CISS1-like phenotype, they do not explain all their clinical manifestations and highlight the high phenotypic heterogeneity associated with mutations in KLHL7.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{marongiu_foxl2_2015,

title = {FOXL2 modulates cartilage, skeletal development and IGF1-dependent growth in mice},

author = {Mara Marongiu and Loredana Marcia and Emanuele Pelosi and Mario Lovicu and Manila Deiana and Yonqing Zhang and Alessandro Puddu and Angela Loi and Manuela Uda and Antonino Forabosco and David Schlessinger and Laura Crisponi},

doi = {10.1186/s12861-015-0072-y},

issn = {1471-213X},

year  = {2015},

date = {2015-07-01},

journal = {BMC developmental biology},

volume = {15},

pages = {27},

abstract = {BACKGROUND: Haploinsufficiency of the FOXL2 transcription factor in humans causes Blepharophimosis/Ptosis/Epicanthus Inversus syndrome (BPES), characterized by eyelid anomalies and premature ovarian failure. Mice lacking Foxl2 recapitulate human eyelid/forehead defects and undergo female gonadal dysgenesis. We report here that mice lacking Foxl2 also show defects in postnatal growth and embryonic bone and cartilage formation. 

METHODS: Foxl2 (-/-) male mice at different stages of development have been characterized and compared to wild type. Body length and weight were measured and growth curves were created. Skeletons were stained with alcian blue and/or alizarin red. Bone and cartilage formation was analyzed by Von Kossa staining and immunofluorescence using anti-FOXL2 and anti-SOX9 antibodies followed by confocal microscopy. Genes differentially expressed in skull vaults were evaluated by microarray analysis. Analysis of the GH/IGF1 pathway was done evaluating the expression of several hypothalamic-pituitary-bone axis markers by RT-qPCR. 

RESULTS: Compared to wild-type, Foxl2 null mice are smaller and show skeletal abnormalities and defects in cartilage and bone mineralization, with down-regulation of the GH/IGF1 axis. Consistent with these effects, we find FOXL2 expressed in embryos at 9.5 dpc in neural tube epithelium, in head mesenchyme near the neural tube, and within the first branchial arch; then, starting at 12.5 dpc, expressed in cartilaginous tissue; and at PO and P7, in hypothalamus. 

CONCLUSIONS: Our results support FOXL2 as a master transcription factor in a spectrum of developmental processes, including growth, cartilage and bone formation. Its action overlaps that of SOX9, though they are antagonistic in female vs male gonadal sex determination but conjoint in cartilage and skeletal development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{palomba_genome-wide_2015,

title = {Genome-wide association study of susceptibility loci for breast cancer in Sardinian population},

author = {Grazia Palomba and Angela Loi and Eleonora Porcu and Antonio Cossu and Ilenia Zara and Mario Budroni and Mariano Dei and Sandra Lai and Antonella Mulas and Nina Olmeo and Maria Teresa Ionta and Francesco Atzori and Gianmauro Cuccuru and Maristella Pitzalis and Magdalena Zoledziewska and Nazario Olla and Mario Lovicu and Marina Pisano and Gon{ç}alo R Abecasis and Manuela Uda and Francesco Tanda and Kyriaki Michailidou and Douglas F Easton and Stephen J Chanock and Robert N Hoover and David J Hunter and David Schlessinger and Serena Sanna and Laura Crisponi and Giuseppe Palmieri},

doi = {10.1186/s12885-015-1392-9},

issn = {1471-2407},

year  = {2015},

date = {2015-05-01},

journal = {BMC cancer},

volume = {15},

pages = {383},

abstract = {BACKGROUND: Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. 

METHODS: We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. 

RESULTS: Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p < 0(-6) level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10(-5), we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16 x 10(-5)), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. 

CONCLUSIONS: This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{palomba_role_2009,

title = {A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population},

author = {Grazia Palomba and Angela Loi and Antonella Uras and Patrizia Fancello and Giovanna Piras and Attilio Gabbas and Antonio Cossu and Mario Budroni and Antonio Contu and Francesco Tanda and Antonio Farris and Sandra Orr{ù} and Carlo Floris and Marina Pisano and Mario Lovicu and Maria Cristina Santona and Gennaro Landriscina and Laura Crisponi and Giuseppe Palmieri and Maria Monne},

doi = {10.1186/1471-2407-9-245},

issn = {1471-2407},

year  = {2009},

date = {2009-07-01},

journal = {BMC cancer},

volume = {9},

pages = {245},

abstract = {BACKGROUND: In recent years, numerous studies have assessed the prevalence of germline mutations in BRCA1 and BRCA2 genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of BRCA1-2 mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of BRCA1-2 germline mutations was also evaluated. 

METHODS: Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for BRCA1-2 mutations by DHPLC analysis and DNA sequencing. Association of BRCA1 and BRCA2 mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test. 

RESULTS AND CONCLUSION: Overall, 8 BRCA1 and 5 BRCA2 deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in BRCA2 gene. The geographical distribution of BRCA1-2 mutations was related to three specific large areas of Sardinia, reflecting its ancient history: a) the Northern area, linguistically different from the rest of the island (where a BRCA2 c.8764_8765delAG mutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (where BRCA2 mutations are still more common than BRCA1 mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of BRCA1-2 germline mutations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}