Department of Molecular Biology

Medical Genetics Laboratory

Coordinator: Prof. Alessandra Renieri

 

La Struttura

 

Coworkers

Dr. Francesca Ariani

  Dr. Mirella Bruttini

  Dr. Ilaria Longo

  Dr. Francesca Mari

  Dr. Ilaria Meloni

  Dr. Chiara Pescucci

 

 

 

 

 

 


 

 Alessandra Renieri, M.D., Ph.D.

Associate Professor in Medical Genetics

 


 


 

 

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M.D. University of Siena, Italy, 1989
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Ph.D. (Medical Genetics). University of Siena, Italy, 1993
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Medical Genetics Specialty degree, University of Florence, Italy, 1998

Click here for a detailed CV 

 

Research activity

My research interests focus on the causes of nephropathy and mental retardation.  For the former, my laboratory is concentrated, since several years, on molecular basis of Alport syndrome, a hereditary nephropathy which may be transmitted both as X-linked as well as an autosomal recessive or autosomal dominant trait. We have performed mutation analysis in both COL4A5 gene on the X chromosome and COL4A3/COL4A4 genes on chromosome 2 in several patients. Our results suggest that the autosomal form of Alport syndrome may be a model between dominant and recessive inheritance, leading to important implications for clinical practice and genetic counseling.

We have identified several novel mutations in MECP2 gene in patients with Rett syndrome, a neurodegenerative disorders affecting young girls.  We have collaborated with Dr. Zappella (Neuropsychiatry, Siena) in an attempt to determine if a genotype/ phenotype correlation exists. We have found that the a benign variant of Rett phenotype, called Presereved Speech Variant, most frequently results from either missense mutations or mutations giving rise to a late truncated form of the MECP2 gene.  We will now attempt to find modifier genes which may change prognosis of these patients. Also, we have recently identified a truncating mutation in MECP2, which causes XLMR in males.  Thus, mutations in this gene give rise to XLMR different from Rett syndrome.

Lastly, we recently identified the FACL4 gene, which encodes a long chain fatty acid synthetase, in Xq22.3 to be responsible for a small percentage of X-linked non specific mental retardation. As there is a enzymatic assay available to examine activity of the protein in blood, we are exploring the possibility of using a screening test in males with MR.               

 

Selected Publications:

 

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Renieri A, Seri M, Myers JC, Pihlajaniemi T, Massella L, Rizzoni G, De Marchi M. De novo mutation in the COL4A5 gene converting glycine 325 to glutamic acid in Alport syndrome. Hum Mol Genet  1: 127-129, 1992.
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Renieri A, Galli L, De Marchi M, Lupo A, Li Volti S, Mollica F, Peissel B, Pignatti PF, Turco AE. Single base pair deletions in exon 39 ans 42 of the COL4A5 gene in Alport syndrome. Hum Mol Genet 3: 201-202, 1994.
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Renieri A, Galli L, Grillo A, Bruttini M, Neri T, Zanelli P, Rizzoni G, Massella L, Sessa A, Meroni M, Peratoner L, Riegler P, Scolari F, Mileti M, Giani M, Cossu M, Savi M, Ballabio A, De Marchi M. Major COL4A5 gene rearrangements in patients with juvenile type Alport syndrome. Am J Med Genet 59: 380-385, 1995.
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Renieri A., Bruttini M., Galli L., Zanelli P., Neri T., Rossetti S., Turco A Heiskari N, Zhou J, Gusmano R, Massella L, Banfi G, Scolari F, Sessa A, Rizzoni G, Tryggvason K, Pignatti PF, Savi M, Ballabio A, De Marchi M. X-linked Alport syndrome: an SSCP-based mutation survey over all 51 exons of the COL4A5 gene. Am J Hum Genet 58:1192-1204, 1996.
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Jonsson J, Renieri A, Gallagher P, Kashtan C.E, Cherniske E.M, Bruttini M, Piccini M, Vitelli F, Ballabio B, Pober B.R. Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis: a new X-linked contiguous gene deletion syndrome? J Med Genet 35: 273-278 1998
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Piccini M, Vitelli F, Bruttini M, Pober B, Jonsson JJ, Villanova M, Zollo M, Borsani G, Ballabio A and Renieri A FACL4, a new gene encoding Long Chain Acyl-CoA Synthetase 4, is deleted in a family with Alport syndrome, elliptocytosis and mental retardation. Genomics 47, 350-358, 1998
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Piccini M, Casari G, Zhou J, Bruttini M, Li Volti S,  Ballabio A,  Renieri A Evidence for genetic heterogeneity in Benign Familial Hematuria Am J Nephrol 19:4: 464-467, 1999
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Vitelli F,  Marcello Villanova,  Alessandro Malandrini, Mirella Bruttini, Monica Piccini, Luciano Merlini, GianCarlo Guazzi, Renieri A. Inheritance of a 38 kb fragment in an apparently sporadic case of facioscapulohumeral muscular dystrophy (FSHD). Muscle Nerve 22: 1437-1441, 1999.
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Bruttini M, Francesca Vitelli, Ilaria Meloni, Giuseppe Rizzari, Mario della Volpe, Gianna Mazzucco, Mario De Marchi and Renieri A. Mosaicism in Alport syndrome and genetic counseling. J Med Genet 37: 717-719, 2000.
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Vitelli F, Meloni I, Fineschi S, Favara F, Storlazzi CT, Rocchi M, Renieri A. Identification and characterization of mouse orthologs of the AMMECR1 and FACL4 genes deleted in AMME syndrome: orthology of Xq22.3 and MmuXF1-F3 Cytogenet Cell Genet 88: 259-263, 2000.
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De Bona C, Zappella M, Hayek G, Meloni I, Vitelli F, Bruttini M, Cusano R, Loffredo P, Longo I, Renieri A. Preserved speech variant is allelic of classic Rett syndrome Eur J Hum Genet 8: 325-330, 2000.
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Ilaria Meloni, Mirella Bruttini , Ilaria Longo , Francesca Mari , Flavio Rizzolio, Patrizia D’Adamo, Koenraad Denvriendt , Jean-Pierre Fryns , Daniela Toniolo and Alessandra Renieri. A mutation in the Rett Syndrome gene, MECP2, causes X-linked mental retardation and progressive spasticity in males. Am J Hum Genet 67(4):982-985, 2000.
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Michele Zappella, Ilaria Meloni, Ilaria Longo, Giuseppe Hayek, Alessandra Renieri. Preserved Speech Variants of the Rett Syndrome: Molecular and Clinical Dissection. Am J Med Genet 104(1): 14-22, 2001
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Ilaria Meloni, Francesca Vitelli, Lucia Pucci, R. Brian Lowry, Rossana Tonlorenzi, Elena Rossi, Mario Ventura, Gianfranco Rizzoni, Clifford E. Kashtan, Barbara Pober, and Alessandra Renieri. Alport syndrome and mental retardation: clinical and genetic dissection of the contiguous gene deletion syndrome in Xq22.3 (ATS-MR). J Med Genet 39:359-365, 2002
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Longo I, Porcedda P, Mari F, Giachino D, Meloni I, Deplano C, Brusco A, Bosio M, Massella L, Lavoratti G, Roccatello D, Frasca’ G, Mazzucco G, Onetti Muda A, Conti M, Fasciolo F, Heidet L, Renieri A and De Marchi M. COL4A3/A4 mutation: from benign familial hematuria to autosomal dominant or recessive Alport S. Kidney Int  61:1947-56 2002.
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Meloni I, Muscettola M, Raynaud M, Longo I, Bruttini M, Moizard M-P, Gomot M, Chelly J, des Portes V, Fryns J-P, Ropers H-H, Yntema H, Lewis SE, Schaffer J and Renieri A. FACL4, encoding fatty acids ligase type 4, is a new MRX gene. Nature Genet 30: 436-440, 2002

Clinical and Diagnostic Activity

As a clinical geneticist, I am actively involved in the evaluation, counseling, and, wherever possible, treatment of adults and children affected by genetic and related disease processes. This activity includes patient evaluation, test interpretation, and genetic counseling with patients and their families. I coordinate the molecular diagnosis for the following specific genetic disorders: Alport syndrome, Facioscapulohumeral dystrophy, Oculopharyngel muscular dystrophy, X-linked ichthyosis, Rett syndrome, X-linked Retinoschisis, Retinoblastoma, X-linked mental retardation (due to FACL4 gene). The identification of a specific mutation in a proband allows rapid and accurate testing of other family members for the same mutation. This information plays a crucial role in genetic counseling and determination of recurrence risk

 

Education activity

 

As Associate Professor in Medical Genetics, I teach Medical Genetics in the course for M.D. degree and in 12 different courses for Medical Specialties (School of Medicine, University of Siena). I am coordinator of a PhD course in Medical Genetics * (click here for more details).