Publications by authors named "Mauro Pierluigi"

32 Publications

The Interaction of Lean Body Mass With Fat Body Mass Is Associated With Vertebral Fracture Prevalence in Women With Early Breast Cancer Undergoing Aromatase Inhibitor Therapy.

JBMR Plus 2021 Feb 21;5(2):e10440. Epub 2020 Dec 21.

Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Medical Oncology University of Brescia, Aziende Socio Sanitarie Territoriali (ASST) Spedali Civili Brescia Italy.

Aromatase inhibitors (AIs) induce depletion of estrogen levels, causing bone loss and increased fracture risk in women with breast cancer. High-fat body mass (FBM) emerged as an independent factor associated with the prevalence of morphometric vertebral fractures (VFs) in patients undergoing AIs. We explored the role of lean body mass (LBM) and the interaction of LBM with FBM in predicting the occurrence of VFs in postmenopausal women who were either AI-naïve or AI-treated. A total of 684 consecutive breast cancer patients were enrolled in this cross-sectional study. Each woman underwent a dual-energy X-ray absorptiometry (DXA) scan, measuring bone mineral density (BMD), LBM, and FBM; VFs were assessed using a quantitative morphometric analysis of DXA images. After propensity score matching, the study population was restricted to 480 women, 240 AI-naïve and 240 AI-treated. We used multivariable logistic regression models to explore the associations between baseline characteristics, VF prevalence and the interaction between LBM, FBM and AI therapy. No interaction between LBM and AI therapy on VF prevalence was shown. Conversely, we reported a significant interaction between LBM, FBM and AI therapy ( = .0311). Among AI-treated women having LBM below and FBM above or equal the median value, VF prevalence was numerically higher (15/31; 48.4%) than in other subgroups (VF prevalence: 35.7% in high-LBM and low-FBM group, 23.2% in high-LBM and high-FBM group, and 19.8% in low-LBM and low-FBM group). Among AI-naïve women, the greatest VF proportion was observed in the subgroup with LBM and FBM below median value (25/92; 27.2%). This study suggests a synergism between LBM and FBM in predicting the morphometric VF in women with early breast cancer undergoing AIs. This observation is new and deserves further investigation. The assessment of body composition by DXA might be useful when estimating fracture risk in this population. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872339PMC
February 2021

Bronchoesophageal Fistula.

N Engl J Med 2020 Dec;383(25):e137

ASST Spedali Civili di Brescia, Brescia, Italy

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http://dx.doi.org/10.1056/NEJMicm2018535DOI Listing
December 2020

Molecular and Immune Biomarkers for Cutaneous Melanoma: Current Status and Future Prospects.

Cancers (Basel) 2020 Nov 20;12(11). Epub 2020 Nov 20.

Laboratory of Immune and Biological Therapy, Research Department, Sidra Medicine, Doha 26999, Qatar.

Advances in the genomic, molecular and immunological make-up of melanoma allowed the development of novel targeted therapy and of immunotherapy, leading to changes in the paradigm of therapeutic interventions and improvement of patients' overall survival. Nevertheless, the mechanisms regulating either the responsiveness or the resistance of melanoma patients to therapies are still mostly unknown. The development of either the combinations or of the sequential treatment of different agents has been investigated but without a strongly molecularly motivated rationale. The need for robust biomarkers to predict patients' responsiveness to defined therapies and for their stratification is still unmet. Progress in immunological assays and genomic techniques as long as improvement in designing and performing studies monitoring the expression of these markers along with the evolution of the disease allowed to identify candidate biomarkers. However, none of them achieved a definitive role in predicting patients' clinical outcomes. Along this line, the cross-talk of melanoma cells with tumor microenvironment plays an important role in the evolution of the disease and needs to be considered in light of the role of predictive biomarkers. The overview of the relationship between the molecular basis of melanoma and targeted therapies is provided in this review, highlighting the benefit for clinical responses and the limitations. Moreover, the role of different candidate biomarkers is described together with the technical approaches for their identification. The provided evidence shows that progress has been achieved in understanding the molecular basis of melanoma and in designing advanced therapeutic strategies. Nevertheless, the molecular determinants of melanoma and their role as biomarkers predicting patients' responsiveness to therapies warrant further investigation with the vision of developing more effective precision medicine.
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http://dx.doi.org/10.3390/cancers12113456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699774PMC
November 2020

Efficacy of the DigniCap System in preventing chemotherapy-induced alopecia in breast cancer patients is not related to patient characteristics or side effects of the device.

Int J Nurs Pract 2020 Sep 22:e12888. Epub 2020 Sep 22.

Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia at ASST Spedali Civili, Brescia, Italy.

Background: The DigniCap System is an effective scalp cooling device for the prevention of chemotherapy-induced alopecia in early breast cancer patients.

Aim: This prospective study was designed to confirm the efficacy and tolerability of the device, to explore potential factors associated with its efficacy and to collect data on patient perceptions and satisfaction.

Methods: Between January 2016 and June 2018, 163 early breast cancer patients eligible for adjuvant chemotherapy were enrolled. Hair loss was assessed using the Dean scale, where a score of 0-2 (hair loss ≤50%) was defined as successful.

Results: Hair preservation was successful in 57% of patients in the overall series. The proportion was even higher (81%) in the patient subgroup treated with a paclitaxel and trastuzumab regimen. Side effects (feeling cold, headache, head heaviness, scalp and cervical pain) were mild to moderate and did not correlate with the rate of hair loss. Lifestyle, anthropometric factors and hair characteristics failed to be associated with device efficacy.

Conclusions: The DigniCap System was well tolerated and found to be effective in preventing alopecia in early breast cancer patients. Our study failed to identify factors other than type of chemotherapy regimen associated with hair preservation.
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http://dx.doi.org/10.1111/ijn.12888DOI Listing
September 2020

Efficacy of Eribulin mesylate in older patients with breast cancer: A pooled analysis of clinical trial and real-world data.

J Geriatr Oncol 2020 07 13;11(6):976-981. Epub 2020 Apr 13.

Oncology Department, Treviglio-Caravaggio Hospital, Treviglio, Italy.

Purpose: Eribulin mesylate (EM) is a non-taxane microtubule inhibitor approved for use in patients with metastatic breast cancer. With this pooled analysis of retrospective studies, we evaluated the efficacy and toxicity profile of EM in older patients with breast cancer in the real-world setting.

Methods: We performed a systematic database search for studies published up to March 2019 and reporting outcome and adverse events with EM in older patients (≥70 years). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) were described and aggregated in a pooled analysis. Main toxicity rates (G1-2 and G3-4) were also described.

Results: The analysis included five studies for a total of 301 patients. The median age was 71 to 74 years. Pooled ORR, median PFS and OS were 23.2%, 4.8 and 13.1 months, respectively. The disease control rate was 47%. Grade 3-4 neutropenia was 0 to 49%, G3-4 anemia and thrombocytopenia were rare. The most frequent G3-4 adverse events among non-hematological toxicities were fatigue (5-16.5%) and neurotoxicity (0-10.1%). Dose reduction rate was reported in three studies and carried out in 40% of patients (18.6-84%).

Conclusions: This pooled analysis shows that the median OS in older patients with breast cancer is 13 months, with an ORR of 23%. Control of disease was achieved in about 50% of patients. Dose reduction was relatively frequent and severe toxicities were rare. EM treatment of older patients with breast cancer is feasible and reflects the outcomes for the general population.
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http://dx.doi.org/10.1016/j.jgo.2020.03.021DOI Listing
July 2020

Expanding the phenotype of reciprocal 1q21.1 deletions and duplications: a case series.

Ital J Pediatr 2017 Jul 19;43(1):61. Epub 2017 Jul 19.

Department of Sciences for Health Promotion and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, Palermo, Italy.

Background: Recurrent reciprocal 1q21.1 deletions and duplications have been associated with variable phenotypes. Phenotypic features described in association with 1q21.1 microdeletions include developmental delay, craniofacial dysmorphism and congenital anomalies. The 1q21.1 reciprocal duplication has been associated with macrocephaly or relative macrocephaly, frontal bossing, hypertelorism, developmental delay, intellectual disability and autism spectrum disorder.

Methods: Our study describes seven patients, who were referred to us for developmental delay/intellectual disability, dysmorphic features and, in some cases, congenital anomalies, in whom we identified 1q21.1 CNVs by array-CGH.

Results: Our data confirm the extreme phenotypic variability associated with 1q21.1 microdeletion and microduplication. We observed common phenotypic features, described in previous studies, but we also described, for the first time, congenital hypothyroidism in association with 1q21.1 deletion and trigonocephaly associated with 1q21.1 duplication.

Conclusions: The aim of this study is to contribute to the definition of the phenotype associated with reciprocal 1q21.1 deletions and duplications.
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http://dx.doi.org/10.1186/s13052-017-0380-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518118PMC
July 2017

4p16.1-p15.31 duplication and 4p terminal deletion in a 3-years old Chinese girl: Array-CGH, genotype-phenotype and neurological characterization.

Eur J Paediatr Neurol 2015 Jul 23;19(4):477-83. Epub 2015 Feb 23.

Department of Sciences for Health Promotion and Mother and Child Care, University of Palermo, Palermo, Italy.

Background: Microscopically chromosome rearrangements of the short arm of chromosome 4 include the two known clinical entities: partial trisomy 4p and deletions of the Wolf-Hirschhorn critical regions 1 and 2 (WHSCR-1 and WHSCR-2, respectively), which cause cranio-facial anomalies, congenital malformations and developmental delay/intellectual disability.

Methods/results: We report on clinical findings detected in a Chinese patient with a de novo 4p16.1-p15.32 duplication in association with a subtle 4p terminal deletion of 6 Mb in size. This unusual chromosome imbalance resulted in WHS classical phenotype, while clinical manifestations of 4p trisomy were practically absent.

Conclusion: This observation suggests the hypothesis that haploinsufficiency of sensitive dosage genes with regulatory function placed in WHS critical region, is more pathogenic than concomitant 4p duplicated segment. Additionally clinical findings in our patient confirm a variable penetrance of major malformations and neurological features in Chinese children despite of WHS critical region's deletion.
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http://dx.doi.org/10.1016/j.ejpn.2015.02.002DOI Listing
July 2015

Microdeletion 2q23.3q24.1: exploring genotype-phenotype correlations.

Congenit Anom (Kyoto) 2015 May;55(2):107-11

Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.

We report a case of a 13-year-old girl with a 5.4 Mb de novo deletion, encompassing bands 2q23.3q24.1, identified by array-comparative genomic hybridization. She presented with minor facial and digital anomalies, mild developmental delay during infancy, and behavioral disorders. Few of the reported cases overlap this deletion and all only partially. We tried to compare the clinical features of the patient with the other cases, even though not all of them were molecularly characterized in detail. Considering the neuropsychiatric involvement of the proband and the clinical descriptions of other similar cases, we attempted to identify the genes more probably involved in neurological development and function in the deleted region, particularly GALNT13, KCNJ3 and NR4A2, which are expressed in neuronal cells.
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http://dx.doi.org/10.1111/cga.12080DOI Listing
May 2015

14q13.1-21.1 deletion encompassing the HPE8 locus in an adolescent with intellectual disability and bilateral microphthalmia, but without holoprosencephaly.

Am J Med Genet A 2012 Jun 11;158A(6):1427-33. Epub 2012 May 11.

Centro di Riferimento Regionale per la Sindrome di Down e le Altre Patologie Cromosomiche e Genetiche-Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.

Interstitial deletions involving 14q13.1q21.1 are rare. In the literature at least 10 cases involving this region have been described and all patients showed a phenotype within the holoprosencephaly (HPE) spectrum. Previous studies suggested the HPE8 region as a candidate locus for HPE at 14q13. We report an adolescent with a 14q13.1q21.1 deletion encompassing the HPE8 region associated with intellectual disability (ID), bilateral microphthalmia, and coloboma, without cerebral anomalies typical of HPE. Except for ocular defects (i.e., microphthalmia, coloboma) consistent with HPE-type anomalies, the minor facial dysmorphia was not suggestive for HPE and the absence of cerebral anomalies should rule out this diagnosis. The deletion of the potential HPE candidate genes NPAS3, EAPP, SNX6, and TULIP1, raises doubts about their pathologic role in determining HPE. It is likely that deletions of HPE genes are not sufficient to cause HPE, and that multiple genetic, chromosomal, and environmental factors interact to determine the variable clinical expression of HPE. This is the first case of a 14q deletion encompassing the HPE8 locus with the only features consistent with HPE-type anomalies affecting the ocular system (i.e., microphthalmia, coloboma), and without cerebral anomalies specific for HPE. The inclusion of potential HPE candidate genes in the deletion raises the question whether this patient is affected by a less severe form of HPE (HPE microform), or whether he has a new ID/MCA deletion syndrome.
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http://dx.doi.org/10.1002/ajmg.a.35334DOI Listing
June 2012

Characterization of a complex rearrangement involving chromosomes 1, 4 and 8 by FISH and array-CGH.

J Appl Genet 2012 Aug 29;53(3):285-8. Epub 2012 Apr 29.

Laboratorio di Genetica Umana, E.O. Ospedali Galliera, Genova, Italy.

Complex chromosomal rearrangements (CCRs) are structural aberrations involving more than two chromosomes with at least three breakpoints. CCRs can be divided into familial and de novo. Balanced CCR are extremely rare in humans and are at high risk of producing unbalanced gametes. Individuals with balanced CCR are usually phenotipically normal but report fertility problems, recurrent miscarriages or congenital anomalies in newborn offsprings as consequence of either meiotic failure or imbalanced chromosomes segregation.We describe the case of an unbalanced CCR involving chromosomes 1, 4 and 8 found in a girl with developmental delay, hexadactilia and microcephaly. The rearrangement, apparently balanced at a standard karyotype analysis and of maternal origin, was demonstrated to be unbalanced by array-CGH and FISH. In conclusion our study underlines the importance of the combined use of a quantitative technique, as array-CGH, to detect criptic segmental aneuploidies, and a qualitative tool, as FISH analysis, to physically map the localization of the chromosome segments involved, in order to realize the exact nature that underlies a chromosomal rearrangement.
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http://dx.doi.org/10.1007/s13353-012-0097-xDOI Listing
August 2012

Interstitial deletion of chromosome 2p15-16.1: report of two patients and critical review of current genotype-phenotype correlation.

Eur J Med Genet 2012 Apr 18;55(4):238-44. Epub 2012 Feb 18.

U.O. Pediatria e TIN Dipartimento Materno-Infantile, Università degli Studi di Palermo via Alfonso Giordano 3, 90127 Palermo, Italy.

Unlabelled: We report two individuals with developmental delay and dysmorphic features, in whom array-based comparative genomic hybridization (array CGH) led to the identification of a 2p15p16.1 de novo deletion. In the first patient (Patient 1) a familial deletion of 6q12, inherited from her father, was also detected. In the second patient (Patient 2) in addition to the 2p15p16.1 microdeletion a de novo deletion in Xq28 was detected. Both individuals shared dysmorphic features and developmental delay with the six reported patients with a 2p15p16.1 microdeletion described in medical literature.

Conclusion: in the first patient a 642 kb 2p16.1 deletion (from 60.604 to 61.246 Mb), and a 930 kb 6q12 familial deletion, was detected and in the second a 2.5 Mb 2p15p16.1 deletion (from 60.258 to 62.763 Mb), with a Xq28 deletion, was discovered. The common dysmorphic features and neurodevelopmental delay found in these patients are in agreement with the clinical phenotype of a microdeletion syndrome involving 2p15p16.1. Our data confirm the hypothesis suggesting that 2p15p16.1 deletion is a contiguous gene syndrome.
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http://dx.doi.org/10.1016/j.ejmg.2012.01.014DOI Listing
April 2012

The first case of myoclonic epilepsy in a child with a de novo 22q11.2 microduplication.

Am J Med Genet A 2011 Dec 14;155A(12):3054-9. Epub 2011 Oct 14.

Dipartimento Materno Infantile, Università di Palermo, Palermo, Italy.

Chromosome 22, particularly the q11.2 sub-band, has long been recognized as responsible for multiple congenital anomaly disorders. In particular, its susceptibility to subtle microdeletions or, more rarely, microduplications has been attributed to the presence of several low-copy repeats spanning the region as mediators of nonallelic homologous recombination that result in 22q11.2 rearrangements. While recent data suggest that the frequency of 22q11.2 microduplications could be approximately half of all deletions, now only 50 unrelated cases have been reported thus far. However, it is reasonable to suppose that microduplications of 22q11.2 may be largely undetected as a result of a less-distinct, unpredictable, and/or milder phenotype ranging from normal to mild learning difficulties with/without other multiple defects. We report on the first case of myoclonic epilepsy in a 10-year-old boy carrying a de novo 22q11.2 microduplication. Emphasizing that this rare association could be one of the many unrecognized aspects underlying this new emerging syndrome and once again its clinical heterogeneity, we suggest further investigation of the function of the RAB36 gene and propose that in the screening of individuals with developmental delay, minor behavioral problems mild dysmorphology and seizures, investigation of 22q11.2 microduplications should be considered.
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http://dx.doi.org/10.1002/ajmg.a.34275DOI Listing
December 2011

A 12.4 Mb direct duplication in 19q12-q13 in a boy with cardiac and CNS malformations and developmental delay.

J Appl Genet 2011 Aug 3;52(3):335-9. Epub 2011 Mar 3.

Neonatology Unit, Department of Mother & Child, University of Modena, Via del Pozzo 71, Modena, Italy.

The interstitial duplication of the long arm of chromosome 19 is a rare abnormality, characterized by developmental delay and dysmorphic features, also reported in association with cardiac, urinary, and CNS malformations. We describe a new case of de novo 19q12-q13.2 duplication characterized by fluorescent in situ hybridization (FISH) and array comparative genomic hybridization (CGH) and, by reviewing the data from previous articles, we report a tentative genotype/phenotype correlation. Four previously described cases showed the same or overlapping 19q duplications and shared with our patient common dysmorphisms, psychomotor retardation, and CNS malformations. The present description of a new case of 19q12-q13.2 duplication with a molecular cytogenetic and genomic characterization adds further elements to the understanding of the impact of the genomic segment on the phenotype.
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http://dx.doi.org/10.1007/s13353-011-0033-5DOI Listing
August 2011

The refinement of the critical region for the 2q31.2q32.3 deletion syndrome indicates candidate genes for mental retardation and speech impairment.

Am J Med Genet B Neuropsychiatr Genet 2010 Oct;153B(7):1342-6

Division of Medical Genetics, Galliera Hospital, Genova, Italy.

Current literature provides more than 30 patients with interstitial deletions in chromosome 2q31q33. Only a few of them were studied using high-resolution methods. Among these, two patients had presented with a particular consistence of some clinical features associated to a deletion between bands q31.2 and q32.3 of chromosome 2. This clinical pattern, labeled as "2q31.2q32.3 syndrome," consists of multiple dysmorphisms, developmental delay, mental retardation and behavioural disturbances. We report an adult female patient with a 4.4 Mb deletion in the 2q31.2q32.3 region, showing facial dysmorphisms, mental retardation and absence of speech. The region overlaps with the deletion found in the two cases previously reported. The critical region points to a few genes, namely NEUROD1, ZNF804A, PDE1A, and ITGA4, which are good candidates to explain the cognitive and behavioural phenotype, as well as the severe speech impairment associated with the 2q31.2q32.3 deletion.
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http://dx.doi.org/10.1002/ajmg.b.31107DOI Listing
October 2010

Array-CGH defined chromosome 1p duplication in a patient with autism spectrum disorder, mild mental deficiency, and minor dysmorphic features.

Am J Med Genet A 2010 Feb;152A(2):486-9

Unità Operativa di Pediatria e Terapia Intensiva Neonatale, Dipartimento Materno Infantile, Università degli Studi di Palermo, Palermo, Italy.

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http://dx.doi.org/10.1002/ajmg.a.33212DOI Listing
February 2010

Array CGH defined interstitial deletion on chromosome 14: a new case.

Eur J Pediatr 2010 Jul 21;169(7):845-51. Epub 2010 Jan 21.

Dipartimento Materno Infantile, Università di Palermo, via Cardinale Rampolla 1, 90142, Palermo, Italy.

Interstitial deletions of the long arm of chromosome 14 are relatively rare. We report a 8.5-year-old girl with dysmorphic facial features and mental retardation associated with a de novo interstitial deletion of chromosome 14. The comparison between our patient and all published patients is reviewed. The genetic investigations have allowed us to define the critical chromosomal region and to start an accurate follow-up.
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http://dx.doi.org/10.1007/s00431-009-1128-4DOI Listing
July 2010

Subtelomeric FISH analysis in 76 patients with syndromic developmental delay/intellectual disability.

Ital J Pediatr 2009 Apr 27;35(1). Epub 2009 Apr 27.

Dipartimento di Scienze Pediatriche, University of Torino, Torino, Italy.

Background: Intellectual disability affects approximately 1 to 3% of the general population. The etiology is still poorly understood and it is estimated that one-half of the cases are due to genetic factors. Cryptic subtelomeric aberrations have been found in roughly 5 to 7% of all cases.

Methods: We performed a subtelomeric FISH analysis on 76 unrelated children with normal standard karyotype ascertained by developmental delay or intellectual disability, associated with congenital malformations, and/or facial dysmorphisms.

Results: Ten cryptic chromosomal anomalies have been identified in the whole cohort (13,16%), 8 in the group of patients characterized by developmental delay or intellectual disability associated with congenital malformations and facial dysmorphisms, 2 in patients with developmental delay or intellectual disability and facial dysmorphisms only.

Conclusion: We demonstrate that a careful clinical examination is a very useful tool for pre-selection of patients for genomic analysis, clearly enhancing the chromosomal anomaly detection rate. Clinical features of most of these patients are consistent with the corresponding emerging chromosome phenotypes, pointing out these new clinical syndromes associated with specific genomic imbalances.
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http://dx.doi.org/10.1186/1824-7288-35-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687548PMC
April 2009

De novo balanced chromosome rearrangements in prenatal diagnosis.

Prenat Diagn 2009 Mar;29(3):257-65

Lab Citogenetica Medica e Genetica Molecolare, IRCCS Ist. Auxologico Italiano, Milano, Italy.

Objective: We surveyed the datasheets of 29 laboratories concerning prenatal diagnosis of de novo apparently balanced chromosome rearrangements to assess the involvement of specific chromosomes, the breakpoints distribution and the impact on the pregnancy outcome.

Method: By means of a questionnaire, data on 269.371 analyses performed from 1983 to 2006 on amniotic fluid, chorionic villus and fetal blood samples were collected.

Results: A total of 246 balanced anomalies were detected at frequencies of 72% for reciprocal translocations, 18% for Robertsonian translocations, 7% for inversions and 3% for complex chromosome rearrangements. The total frequencies of balanced rearrangements were 0.09%, 0.08% and 0.05% on amniotic fluid, chorionic villus and fetal blood samples.

Conclusion: A preferential involvement of chromosomes 22, 7, 21, 3, 9 and 11 and a less involvement of chromosomes X, 19, 12, 6 and 1 was observed. A nonrandom distribution of the breakpoints across chromosomes was noticed. Association in the location of recurrent breakpoints and fragile sites was observed for chromosomes 11, 7, 10 and 22, while it was not recorded for chromosome 3. The rate of pregnancy termination was about 20%, with frequencies decreasing from complex chromosomal rearrangements (33%), reciprocal translocations (24%) to inversions (11%) and Robertsonian translocations (3%).
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http://dx.doi.org/10.1002/pd.2215DOI Listing
March 2009

10qter deletion: a new case.

Am J Med Genet A 2008 Sep;146A(18):2435-8

Dipartimento Materno Infantile, Università di Palermo, Palermo, Italy.

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http://dx.doi.org/10.1002/ajmg.a.32467DOI Listing
September 2008

A case of autism with an interstitial 1q deletion (1q23.3-24.2) and a de novo translocation of chromosomes 1q and 5q.

Am J Med Genet A 2007 Nov;143A(22):2733-7

Medical Genetics Department, Gaetano Rummo Hospital, Benevento, Italy.

Chromosomal abnormalities may cause autism by disrupting a gene or by providing a permissive genetic environment for mutations elsewhere in the genome to become expressed as autism. We report here on a patient with an apparently balanced de novo translocation of chromosomes 1q and 5q. He presented with minor dysmorphic features and renal malformations, mental retardation, and autism. Further characterization of the chromosomal rearrangement by FISH revealed a deletion in chromosome 1 from q23.3 to q24.2 corresponding to a region of rising interest in the research of autism susceptibility genes. The array-CGH technique gave better resolution of the breakpoints and the size of the deletion was calculated to be 4.97 Mb.
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http://dx.doi.org/10.1002/ajmg.a.32006DOI Listing
November 2007

Familial robertsonian 13;14 translocation with mental retardation and epilepsy.

J Child Neurol 2006 Jun;21(6):531-3

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

Familial reports of a robertsonian translocation in more than two generations are rare. We report three generations (a daughter, the mother, and the mother's father) with a heterozygous, balanced robertsonian translocation t(13;14)(q11;q11). Central nervous system disease was present, but differentially expressed, in generations I and III. The daughter presented with mental delay and epilepsy, and the mother was apparently healthy, whereas the mother's father was again symptomatic, with borderline intelligence. Fluorescent in situ hybridization analysis was performed to exclude a loss or gain of chromosomal material. No uniparental disomy was present. We concluded that genetic counseling in the presence of this rearrangement was extremely difficult, independent of the affected parent being symptomatic or asymptomatic.
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http://dx.doi.org/10.1177/08830738060210060701DOI Listing
June 2006

Clinical phenotype and molecular characterization of 6q terminal deletion syndrome: Five new cases.

Am J Med Genet A 2006 Sep;140(18):1944-9

Neuromuscular and Neurodegenerative Disease Unit, "G. Gaslini" Institute, University of Genova, Genova, Italy.

Mental retardation, facial dysmorphisms, seizures, and brain abnormalities are features of 6q terminal deletions. We have ascertained five patients with 6q subtelomere deletions (four de novo, one as a result of an unbalanced translocation) and determined the size of the deletion ranging from 3 to 13 Mb. Our patients showed a recognizable phenotype including mental retardation, characteristic facial appearance, and a distinctive clinico-neuroradiological picture. Focal epilepsy with consistent electroencephalographic features and with certain brain anomalies on neuroimaging studies should suggest 6q terminal deletion. The awareness of the distinctive clinical picture will help in the diagnosis of this chromosomal abnormality.
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http://dx.doi.org/10.1002/ajmg.a.31435DOI Listing
September 2006

6q terminal deletion syndrome associated with a distinctive EEG and clinical pattern: a report of five cases.

Epilepsia 2006 May;47(5):830-8

Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina, Enna, Italy.

Purpose: Mental retardation, facial dysmorphisms, and neurologic and brain abnormalities are features of 6q terminal deletions. Epilepsy is frequently associated with this chromosome abnormality, but electroclinical findings are not well delineated. We report five unrelated patients with 6q terminal deletions and a peculiar clinical, EEG, and neuroradiologic picture of epilepsy, mental retardation, and colpocephaly.

Methods: These three male and two female patients underwent general and neurologic examinations, repeated awake and sleep EEGs, and brain magnetic resonance imaging (MRI). A cytogenetic study and fluorescent in situ hybridization (FISH) with chromosome-specific subtelomeric probes were carried out in all cases.

Results: All subjects had seizures characterized by vomiting, cyanosis, and head and eye version, with and without loss of consciousness. In four cases, EEGs showed posterior spike-and-wave complexes, which were activated by sleep. No patient had status epilepticus or prolonged seizures. Brain MRI revealed colpocephaly and dysgenesis of the corpus callosum and brainstem in four patients; three of them also had hypertrophic massa intermedia. FISH analysis revealed a 6q terminal deletion in all patients, which ranged between 9 Mb (cases 2 and 3) and 16 Mb (case 4).

Conclusions: We suggest that epilepsy associated with 6q terminal deletions is a new entity. Patients with dysmorphic features associated with focal occipital epilepsy, colpocephaly, and dysgenesis of the corpus callosum, thalami, and brainstem should be considered candidates for testing for 6q subtelomere deletions.
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http://dx.doi.org/10.1111/j.1528-1167.2006.00522.xDOI Listing
May 2006

Phenotype resembling Donnai-Barrow syndrome in a patient with 9qter;16qter unbalanced translocation.

Am J Med Genet A 2006 Apr;140(8):892-4

Dipartimento di Scienze Pediatriche, Universita' di Torino, Torino, Italy.

We describe a 3-year-old boy with complete agenesis of corpus callosum, developmental delay/mental retardation, anterior diaphragmatic hernia, Morgagni type, severe hypermetropia, and facial dysmorphism suggesting the diagnosis of Donnai-Barrow syndrome. Subtelomeric FISH analysis revealed a paternally-derived t(9;16) (q34.3;q24.3) translocation with partial 9q monosomy and partial 16q trisomy. As some facial features resemble the 9q emerging phenotype, we suggest the hypothesis that some patients with Donnai-Barrow syndrome might be abscribed to 9q terminal deletion.
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http://dx.doi.org/10.1002/ajmg.a.31188DOI Listing
April 2006

The natural history of Cri du Chat Syndrome. A report from the Italian Register.

Eur J Med Genet 2006 Sep-Oct;49(5):363-83. Epub 2006 Jan 13.

Paediatrics Department and Genetics Unit, S. Andrea Hospital, corso M. Abbiate, 21, 13100 Vercelli, Italy.

The aim of this report is to provide an update on the natural history of the Cri du Chat Syndrome by means of the Italian Register (I.R.). Two hundred twenty patients were diagnosed by standard cytogenetic methods and 112 of these were also characterised by molecular-cytogenetic investigation (FISH). FISH analysis showed interstitial deletions, short terminal deletions and other rare rearrangements not previously correctly diagnosed by standard cytogenetics. The diagnosis was made in the first month of life in 42% and within first year in 82% of cases. The remaining 18% were diagnosed at an age ranging from 13 months to 47 years. At the last follow-up, patient age ranged from 8 months to 61 years. Mortality, already low, has decreased over time as it is lower between 1984-2002 compared to 1965-1983. Mortality was higher in patients with unbalanced translocations resulting in 5p deletions. Our data confirm that the cat-like cry and peculiar timbre of voice are the most typical signs of the syndrome, not only at birth but also later and these are the only signs which might suggest the diagnosis in patients with small deletions and mild clinical picture. A cytogenetic and clinical variability must be underlined. Cardiac, cerebral, renal and gastrointestinal malformations were more frequent in the patients with unbalanced translocations resulting in 5p deletions. Sucking and feeding difficulties and respiratory infections are frequent in the first months or years of life. Intubation difficulties linked to larynx anomalies must be considered. Psychomotor development is delayed in all patients but there is a variability related to deletion size and type as well as other genetic and environmental factors. However, the results showed an improvement in the acquisition of the development skills and progress in social introduction which should encourage caregivers and parents to work together in carrying out the rehabilitative and educational interventions.
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http://dx.doi.org/10.1016/j.ejmg.2005.12.004DOI Listing
November 2006

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

Cytogenetic and molecular evaluation of 241 small supernumerary marker chromosomes: cooperative study of 19 Italian laboratories.

Genet Med 2005 Nov-Dec;7(9):620-5

Department of Experimental, Environmental Medicine, University Milan-Bicocca, Monza, Italy.

Purpose: We evaluated the experiences of 19 Italian laboratories concerning 241 small supernumerary marker chromosomes (sSMCs) with the aim of answering questions arising from their origin from any chromosome, their variable size and genetic content, and their impact on the carrier's phenotype.

Methods: Conventional protocols were used to set up the cultures and chromosome preparations. Both commercial and homemade probes were used for the fluorescent in situ hybridization analyses.

Results: A total of 113 of the 241 sSMCs were detected antenatally, and 128 were detected postnatally. There were 52 inherited and 172 de novo cases. Abnormal phenotype was present in 137 cases (57%), 38 of which were antenatally diagnosed. A mosaic condition was observed in 87 cases (36%). In terms of morphology, monocentric and dicentric bisatellited marker chromosomes were the most common, followed by monocentric rings and short-arm isochromosomes. The chromosomes generating the sSMCs were acrocentric in 132 cases (69%) and non-acrocentric chromosomes in 60 cases (31%); a neocentromere was hypothesized in three cases involving chromosomes 6, 8, and 15.

Conclusion: The presented and published data still do not allow any definite conclusions to be drawn concerning karyotype-phenotype correlations. Only concerted efforts to characterize molecularly the sSMCs associated or not with a clinical phenotype can yield results suitable for addressing karyotype-phenotype correlations in support of genetic counseling.
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http://dx.doi.org/10.1097/01.gim.0000182876.57766.2dDOI Listing
June 2006