Publications by authors named "Maria M de Santi"

7 Publications

  • Page 1 of 1

International consensus guideline for reporting transmission electron microscopy results in the diagnosis of primary ciliary dyskinesia (BEAT PCD TEM Criteria).

Eur Respir J 2020 04 16;55(4). Epub 2020 Apr 16.

Sorbonne Université, Faculté de Médecine, INSERM UMR_S933, (APHP) Assistance Publique Hôpitaux de Paris and CHIC (Centre Hospitalier Intercommunal de Créteil), Paris, France.

Primary ciliary dyskinesia (PCD) is a heterogeneous genetic condition. European and North American diagnostic guidelines recommend transmission electron microscopy (TEM) as one of a combination of tests to confirm a diagnosis. However, there is no definition of what constitutes a defect or consensus on reporting terminology. The aim of this project was to provide an internationally agreed ultrastructural classification for PCD diagnosis by TEM.A consensus guideline was developed by PCD electron microscopy experts representing 18 centres in 14 countries. An initial meeting and discussion were followed by a Delphi consensus process. The agreed guideline was then tested, modified and retested through exchange of samples and electron micrographs between the 18 diagnostic centres.The final guideline a) provides agreed terminology and a definition of Class 1 defects which are diagnostic for PCD; b) identifies Class 2 defects which can indicate a diagnosis of PCD in combination with other supporting evidence; c) describes features which should be included in a ciliary ultrastructure report to assist multidisciplinary diagnosis of PCD; and d) defines adequacy of a diagnostic sample.This tested and externally validated statement provides a clear guideline for the diagnosis of PCD by TEM which can be used to standardise diagnosis internationally.
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http://dx.doi.org/10.1183/13993003.00725-2019DOI Listing
April 2020

Primary cilium alterations and expression changes of Patched1 proteins in niemann-pick type C disease.

J Cell Physiol 2018 Jan 19;233(1):663-672. Epub 2017 May 19.

Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.

Niemann-Pick type C disease (NPC) is a disorder characterized by abnormal intracellular accumulation of unesterified cholesterol and glycolipids. Two distinct disease-causing genes have been isolated, NPC1 and NPC2. The NPC1 protein is involved in the sorting and recycling of cholesterol and glycosphingolipids in the late endosomal/lysosomal system. It has extensive homology with the Patched1 (Ptc1) receptor, a transmembrane protein localized in the primary cilium, and involved in the Hedgehog signaling (Shh) pathway. We assessed the presence of NPC1 and Ptc1 proteins and evaluated the relative distribution and morphology of primary cilia in fibroblasts from five NPC1 patients and controls, and in normal fibroblasts treated with 3-ß-[2-(diethylamino)ethoxy]androst-5-en-17-one (U18666A), a cholesterol transport-inhibiting drug that is widely used to mimic NPC. Immunofluorescence and western blot analyses showed a significant decrease in expression of NPC1 and Ptc1 in NPC1 fibroblasts, while they were normally expressed in U18666A-treated fibroblasts. Moreover, fibroblasts from NPC1 patients and U18666A-treated cells showed a lower percentage distribution of primary cilia and a significant reduction in median cilia length with respect to controls. These are the first results demonstrating altered cytoplasmic expression of Ptc1 and reduced number and length of primary cilia, where Ptc1 is located, in fibroblasts from NPC1 patients. We suggest that the alterations in Ptc1 expression in cells from NPC1 patients are closely related to NPC1 expression deficit, while the primary cilia alterations observed in NPC1 and U18666A-treated fibroblasts may represent a secondary event derived from a defective metabolic pathway.
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http://dx.doi.org/10.1002/jcp.25926DOI Listing
January 2018

Nasal scraping in diagnosing ciliary dyskinesia.

Am J Rhinol 2007 Nov-Dec;21(6):702-5

Ear, Nose, and Throat Department, University of Siena, Siena, Italy.

Background: Primary ciliary dyskinesia (PCD) is a congenital, clinically and ultrastructurally heterogeneous disease caused by abnormal structure and/or function of cilia. Kartagener's syndrome is one subgroup of PCD. Acquired ciliary dyskinesia is frequent, generally being associated with or following respiratory tract infections.

Methods: From January 2003 to April 2006, nasal mucociliary transport time was measured in 64 patients and specimens obtained by nasal scraping were examined by transmission electron microscope (TEM).

Results: The 64 nasal scrapings led to the diagnosis of 11 (17.2%) cases of PCD and 51 (79.7%) cases of secondary ciliary disorder. In two cases (3.1%) no clear diagnosis was possible.

Conclusion: Nasal scraping is an easy, cheap, and efficient tool for detecting ciliary abnormalities by TEM and for distinguishing acquired and congenital modifications.
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http://dx.doi.org/10.2500/ajr.2007.21.3107DOI Listing
March 2008

Hypohidrotic ectodermal dysplasia and intrathoracic neuroblastoma.

Pediatr Dermatol 2007 May-Jun;24(3):267-71

Department of Pediatrics, Section of Pediatric Neurology, Policlinico Le Scotte, University of Siena, Siena, Italy.

We report a 6-year-old girl with a subtle form of hypohidrotic ectodermal dysplasia and a phenotype consisting of curly hair, a round face, a stocky build, and obesity, which was associated with intrathoracic neuroblastoma. Although this new association could be a chance occurrence, its description may alert physicians to look for similar combinations and report these, as it may lead to better syndrome delineation, and patient care.
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http://dx.doi.org/10.1111/j.1525-1470.2007.00400.xDOI Listing
July 2007

Kabuki syndrome with trichrome vitiligo, ectodermal defect and hypogammaglobulinemia A and G.

Brain Dev 2007 Jul 14;29(6):373-6. Epub 2006 Dec 14.

Department of Pediatrics, Section of Neurology, Policlinico Le Scotte, University of Siena, Siena, Italy.

We report a unique combination of symptoms in a case of Kabuki syndrome (KS), a multiple malformation/mental retardation syndrome that has a prevalence of 1:32,000 to 1:86,000. The patient was a mentally delayed 12-year-old male with trichrome vitiligo, ectodermal defect, and hypogammaglobulinemia A and G. This unique combination of signs, described here for the first time, indicates that KS comprises multiple deficits that affect not only the brain, but ectoderm-derived structures and the immune system as well. Our report may provide important clues for understanding the pathogenesis of the KS.
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http://dx.doi.org/10.1016/j.braindev.2006.11.004DOI Listing
July 2007

Global developmental delay, osteopenia and ectodermal defect: a new syndrome.

Brain Dev 2006 Apr 20;28(3):155-61. Epub 2005 Dec 20.

Department of Paediatrics, Obstetrics and Reproductive Medicine, Section of Paediatrics, Policlinico Le Scotte, University of Siena, Siena, Italy.

Unlabelled: Global developmental delay is a serious social problem. It is often unrecognized and the phenotypes are inadequately studied. To investigate the phenotypes of children with aspecific central nervous system (CNS) impairment (poor speech, maladaptive behavioral symptoms such as temper tantrums, aggressiveness, poor concentration and attention, impulsiveness, and mental retardation).

Setting: Tertiary care hospital.

Patients: Three children (two male siblings, and one unrelated girl).

Methods: We used the results from clinical neurological evaluations; imaging and electrodiagnostic studies; metabolic and genetic tests; skin biopsies and bone mineral densitometry. All three children suffered from (A) global developmental delay, (B) osteopenia, and (C) identical skin defects. The skin ultrastructural abnormalities were abnormal keratin differentiation, consisting of hyperkeratosis and granular layer thickening; sweat gland abnormalities, consisting of focal, cytoplasmic clear changes in eccrine secretory cells; and melanocyte abnormalities, with both morphological changes (reduced number and size without evident dendritic processes), and functional changes (defects in the migration of melanosomes in the keratinocytes). These patients present a previously unrecognized syndrome. We retain useful to report this new association, to be recognized, in the next future, as a specific key-sign of a well-defined genetic defect.
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http://dx.doi.org/10.1016/j.braindev.2005.06.011DOI Listing
April 2006