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Dive into the research topics where Patrizia Pappi is active.

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Featured researches published by Patrizia Pappi.


The Journal of Molecular Diagnostics | 2005

An Enhanced Polymerase Chain Reaction Assay to Detect Pre- and Full Mutation Alleles of the Fragile X Mental Retardation 1 Gene

Alessandro Saluto; Alessandro Brussino; Flora Tassone; Carlo Arduino; Claudia Cagnoli; Patrizia Pappi; Paul J. Hagerman; Nicola Migone

Several diagnostic strategies have been applied to the detection of FMR1 gene repeat expansions in fragile X syndrome. Here, we report a novel polymerase chain reaction-based strategy using the Expand Long Template PCR System (Roche Diagnostics, Mannheim, Germany) and the osmolyte betaine. Repeat expansions up to approximately 330 CGGs in males and up to at least approximately 160 CGGs in carrier women could be easily visualized on ethidium bromide agarose gels. We also demonstrated that fluorescence analysis of polymerase chain reaction products was a reliable tool to verify the presence of premutation and full mutation alleles both in males and in females. This technique, primarily designed to detect premutation alleles, can be used as a routine first screen for expanded FMR1 alleles.


Human Mutation | 2010

Missense mutations in the AFG3L2 proteolytic domain account for ∼1.5% of European autosomal dominant cerebellar ataxias

Claudia Cagnoli; Giovanni Stevanin; Alessandro Brussino; Marco Barberis; Cecilia Mancini; Russell L. Margolis; Susan E. Holmes; Marcello Nobili; Sylvie Forlani; Sergio Padovan; Patrizia Pappi; Cécile Zaros; Isabelle Leber; Pascale Ribai; Luisa Pugliese; Corrado Assalto; Alexis Brice; Nicola Migone; Alexandra Durr

Spinocerebellar ataxia type 28 is an autosomal dominant form of cerebellar ataxia (ADCA) caused by mutations in AFG3L2, a gene that encodes a subunit of the mitochondrial m‐AAA protease. We screened 366 primarily Caucasian ADCA families, negative for the most common triplet expansions, for point mutations in AFG3L2 using DHPLC. Whole‐gene deletions were excluded in 300 of the patients, and duplications were excluded in 129 patients. We found six missense mutations in nine unrelated index cases (9/366, 2.6%): c.1961C>T (p.Thr654Ile) in exon 15, c.1996A>G (p.Met666Val), c.1997T>G (p.Met666Arg), c.1997T>C (p.Met666Thr), c.2011G>A (p.Gly671Arg), and c.2012G>A (p.Gly671Glu) in exon 16. All mutated amino acids were located in the C‐terminal proteolytic domain. In available cases, we demonstrated the mutations segregated with the disease. Mutated amino acids are highly conserved, and bioinformatic analysis indicates the substitutions are likely deleterious. This investigation demonstrates that SCA28 accounts for ∼3% of ADCA Caucasian cases negative for triplet expansions and, in extenso, to ∼1.5% of all ADCA. We further confirm both the involvement of AFG3L2 gene in SCA28 and the presence of a mutational hotspot in exons 15–16. Screening for SCA28, is warranted in patients who test negative for more common SCAs and present with a slowly progressive cerebellar ataxia accompanied by oculomotor signs. Hum Mutat 31:1–8, 2010.


Haematologica | 2012

High frequency of ribosomal protein gene deletions in Italian Diamond-Blackfan anemia patients detected by multiplex ligation-dependent probe amplification assay.

Paola Quarello; Emanuela Garelli; Adriana Carando; Cecilia Mancini; Patrizia Pappi; Luciana Vinti; Johanna Svahn; Irma Dianzani; Ugo Ramenghi

Diamond-Blackfan anemia is an autosomal dominant disease due to mutations in nine ribosomal protein encoding genes. Because most mutations are loss of function and detected by direct sequencing of coding exons, we reasoned that part of the approximately 50% mutation negative patients may have carried a copy number variant of ribosomal protein genes. As a proof of concept, we designed a multiplex ligation-dependent probe amplification assay targeted to screen the six genes that are most frequently mutated in Diamond-Blackfan anemia patients: RPS17, RPS19, RPS26, RPL5, RPL11, and RPL35A. Using this assay we showed that deletions represent approximately 20% of all mutations. The combination of sequencing and multiplex ligation-dependent probe amplification analysis of these six genes allows the genetic characterization of approximately 65% of patients, showing that Diamond-Blackfan anemia is indisputably a ribosomopathy.


American Journal of Medical Genetics Part A | 2009

HDR Syndrome : A Novel de novo Mutation in GATA3 Gene

Silvio Ferraris; Angelo Del Monaco; Emanuela Garelli; Adriana Carando; Barbara De Vito; Patrizia Pappi; Roberto Lala; Alberto Ponzone

Human GATA3 haploinsufficiency leads to HDR (hypoparathyroidism, deafness, and renal dysplasia) syndrome. The development of a specific subset of organs in which this transcription factor is expressed appears exquisitely sensitive to gene dosage. We report on a 14‐year‐old patient with symptomatic hypoparathyroidism, sensorineural bilateral deafness, unilateral renal dysplasia, bilateral palpebral ptosis, and horizontal nystagmus. Fundoscopy displayed symmetrical pseudopapilledema, and brain CT scan revealed basal ganglia calcifications. FISH analysis did not disclose any microdeletion in the 22q11.2 or 10p14 regions. GATA3 mutation analysis identified a heterozygous deletion of GG nucleotides at codon 36 and 37 (c.108_109delGG) in exon 2 causing a frameshift with a premature stop codon after a new 15‐aminoacid sequence. Restriction endonuclease analysis performed in parents was negative. Our patient carries a novel “de novo” GATA3 mutation, providing further evidence that HDR syndrome is caused by haploinsufficiency of GATA3, which may be responsible for a complex neurologic picture besides the known triad.


Annals of Human Genetics | 2007

Large Genomic Mutations within the ATM Gene Detected by MLPA, Including a Duplication of 41 kb from Exon 4 to 20

Simona Cavalieri; Ada Funaro; Patrizia Pappi; Nicola Migone; Richard A. Gatti

Mutation detection remains problematic for large genes, primarily because PCR‐based methodology fails to detect heterozygous deletions and any duplication. In the ATM gene only a handful of multi‐exon deletions have been described to date, and this type of mutation has been considered rare. To address this issue we tested a new MLPA (Multiplex Ligation Probe Amplification) kit that covers 33 of the 66 ATM exons, using for controls two previously characterized genomic deletions in addition to three A‐T patients, taken from a survey of nine, who had missing four mutations unidentified after conventional mutation screening. We identified for the first time: 1) a ∼41 kb genomic duplication spanning exons 4–20 (c.‐30_2816dup41kb)(a.k.a., ATM dup 41 kb); 2) a novel genomic deletion including exon 31, and 3) in hemizygosis a point mutation in the non‐deleted exon 31. In this study we extended mutation detection to nine new Italian A‐T patients, using a combined approach of haplotype analysis, DHPLC and MLPA. Overall we achieved a mutation detection rate of >97%, and can now define a spectrum of ATM mutations based on twenty‐one consecutive Italian families with A‐T.


Haematologica | 2008

Multiplex ligation-dependent probe amplification enhances molecular diagnosis of Diamond-Blackfan anemia due to RPS19 deficiency

Paola Quarello; Emanuela Garelli; Adriana Carando; Patrizia Pappi; Marco Barberis; Valentina Coletti; Maria Francesca Campagnoli; Irma Dianzani; Ugo Ramenghi

Diamond-Blackfan anemia (DBA,#MIM105650) is a rare congenital pure red cell aplasia characterized by nor-mochromic macrocytic anemia, reticulocytopenia, and normocellular bone marrow with a selective deficiency of erythroid precursors. Defects in the RPS19 gene on chromosome 19q13.2 are the main


Molecular Cytogenetics | 2014

Large cryptic genomic rearrangements with apparently normal karyotypes detected by array-CGH

Eleonora Di Gregorio; Elisa Savin; Elisa Biamino; E Belligni; Valeria Giorgia Naretto; Gaetana D’Alessandro; Giorgia Gai; Franco Fiocchi; Alessandro Calcia; Cecilia Mancini; Elisa Giorgio; Simona Cavalieri; Flavia Talarico; Patrizia Pappi; Marina Gandione; Monica Grosso; Valentina Asnaghi; Gabriella Restagno; Giorgia Mandrile; Giovanni Botta; Margherita Silengo; Enrico Grosso; Giovanni Battista Ferrero

BackgroundConventional karyotyping (550 bands resolution) is able to identify chromosomal aberrations >5-10 Mb, which represent a known cause of intellectual disability/developmental delay (ID/DD) and/or multiple congenital anomalies (MCA). Array-Comparative Genomic Hybridization (array-CGH) has increased the diagnostic yield of 15-20%.ResultsIn a cohort of 700 ID/DD cases with or without MCA, including 15 prenatal diagnoses, we identified a subgroup of seven patients with a normal karyotype and a large complex rearrangement detected by array-CGH (at least 6, and up to 18 Mb). FISH analysis could be performed on six cases and showed that rearrangements were translocation derivatives, indistinguishable from a normal karyotype as they involved a similar band pattern and size. Five were inherited from a parent with a balanced translocation, whereas two were apparently de novo. Genes spanning the rearrangements could be associated with some phenotypic features in three cases (case 3: DOCK8; case 4: GATA3, AKR1C4; case 6: AS/PWS deletion, CHRNA7), and in two, likely disease genes were present (case 5: NR2F2, TP63, IGF1R; case 7: CDON). Three of our cases were prenatal diagnoses with an apparently normal karyotype.ConclusionsLarge complex rearrangements of up to 18 Mb, involving chromosomal regions with similar size and band appearance may be overlooked by conventional karyotyping. Array-CGH allows a precise chromosomal diagnosis and recurrence risk definition, further confirming this analysis as a first tier approach to clarify molecular bases of ID/DD and/or MCA. In prenatal tests, array-CGH is confirmed as an important tool to avoid false negative results due to karyotype intrinsic limit of detection.


Clinical Genetics | 2017

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.

Evelise Riberi; E Belligni; Elisa Biamino; Malte Spielmann; Ugo Ala; Alessandro Calcia; Irene Bagnasco; D. Carli; Giorgia Gai; M. Giordano; Andrea Guala; R. Keller; Giorgia Mandrile; Carlo Arduino; A. Maffè; Valeria Giorgia Naretto; Fabio Sirchia; Lorena Sorasio; S. Ungari; Andrea Zonta; G. Zacchetti; Flavia Talarico; Patrizia Pappi; Simona Cavalieri; Elisa Giorgio; Cecilia Mancini; Marta Ferrero; Alessandro Brussino; Elisa Savin; Marina Gandione

Array‐comparative genomic hybridization (array‐CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID).


American Journal of Medical Genetics | 2016

A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity

Elisa Biamino; Eleonora Di Gregorio; E Belligni; Roberto Keller; Evelise Riberi; Marina Gandione; Alessandro Calcia; Cecilia Mancini; Elisa Giorgio; Simona Cavalieri; Patrizia Pappi; Flavia Talarico; Antonio Maria Fea; Silvia De Rubeis; Margherita Silengo; Giovanni Battista Ferrero

Copy number variation (CNV) has been associated with a variety of neuropsychiatric disorders, including intellectual disability/developmental delay (ID/DD), autism spectrum disorder (ASD), and schizophrenia (SCZ). Often, individuals carrying the same pathogenic CNV display high clinical variability. By array‐CGH analysis, we identified a novel familial 3q29 deletion (1.36 Mb), centromeric to the 3q29 deletion region, which manifests with variable expressivity. The deletion was identified in a 3‐year‐old girl diagnosed with ID/DD and autism and segregated in six family members, all affected by severe psychiatric disorders including schizophrenia, major depression, anxiety disorder, and personality disorder. All individuals carrying the deletion were overweight or obese, and anomalies compatible with optic atrophy were observed in three out of four cases examined. Amongst the 10 genes encompassed by the deletion, the haploinsufficiency of Optic Atrophy 1 (OPA1), associated with autosomal dominant optic atrophy, is likely responsible for the ophthalmological anomalies. We hypothesize that the haploinsufficiency of ATPase type 13A4 (ATP13A4) and/or Hairy/Enhancer of Split Drosophila homolog 1 (HES1) contribute to the neuropsychiatric phenotype, while HES1 deletion might underlie the overweight/obesity. In conclusion, we propose a novel contiguous gene syndrome due to a proximal 3q29 deletion variably associated with autism, ID/DD, psychiatric traits and overweight/obesity.


European Journal of Medical Genetics | 2017

A case of Feingold type 2 syndrome associated with keratoconus refines keratoconus type 7 locus on chromosome 13q

Fabio Sirchia; Eleonora Di Gregorio; Gabriella Restagno; Enrico Grosso; Patrizia Pappi; Flavia Talarico; Elisa Savin; Simona Cavalieri; Elisa Giorgio; Cecilia Mancini; Barbara Pasini; Jodhbir S. Mehta

We report on a 58-year old woman with microcephaly, mild dysmorphic features, bilateral keratoconus, digital abnormalities, short stature and mild cognitive delay. Except for keratoconus, the phenotype was suggestive for Feingold syndrome type 2 (FGLDS2, MIM 614326), a rare autosomal dominant disorder described in six patients worldwide, due to the haploinsufficiency of MIR17HG, a micro RNA encoding gene. Karyotype showed a de novo deletion on chromosome 13q, further defined by array-Comparative Genomic Hybridization (a-CGH) to a 17.2-Mb region. The deletion included MIR17HG, as expected by the FGLDS2 phenotype, and twelve genes from the keratoconus type 7 locus. Because our patient presented with keratoconus, we propose she further refines disease genes at this locus. Among previously suggested candidates, we exclude DOCK9 and STK24, and propose as best candidates IPO5, DNAJC3, MBNL2 and RAP2A. In conclusion, we report a novel phenotypic association of Feingold syndrome type 2 and keratoconus, a likely contiguous gene syndrome due to a large genomic deletion on 13q spanning MIR17HG and a still to be identified gene for keratoconus.

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