Publications by authors named "Anna Paola Capra"

9 Publications

  • Page 1 of 1

8p23.2-pter Microdeletions: Seven New Cases Narrowing the Candidate Region and Review of the Literature.

Genes (Basel) 2021 Apr 27;12(5). Epub 2021 Apr 27.

Istituto Auxologico Italiano, IRCCS, Laboratory of Medical Cytogenetics and Molecular Genetics, 20145 Milan, Italy.

To date only five patients with 8p23.2-pter microdeletions manifesting a mild-to-moderate cognitive impairment and/or developmental delay, dysmorphisms and neurobehavioral issues were reported. The smallest microdeletion described by Wu in 2010 suggested a critical region (CR) of 2.1 Mb including several genes, out of which , , , and are the main candidates. Here we present seven additional patients with 8p23.2-pter microdeletions, ranging from 71.79 kb to 4.55 Mb. The review of five previously reported and nine Decipher patients confirmed the association of the CR with a variable clinical phenotype characterized by intellectual disability/developmental delay, including language and speech delay and/or motor impairment, behavioral anomalies, autism spectrum disorder, dysmorphisms, microcephaly, fingers/toes anomalies and epilepsy. Genotype analysis allowed to narrow down the 8p23.3 candidate region which includes only , and genes, accounting for the main signs of the broad clinical phenotype associated to 8p23.2-pter microdeletions. This region is more restricted compared to the previously proposed CR. Overall, our data favor the hypothesis that is the actual strongest candidate for neurodevelopmental/behavioral phenotypes. Additional patients will be necessary to validate the pathogenic role of and better define how the two contiguous genes, and , might contribute to the clinical phenotype.
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http://dx.doi.org/10.3390/genes12050652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146486PMC
April 2021

CNVs inform the biological network of Autism spectrum disorder.

Psychiatry Res 2021 03 21;297:113729. Epub 2021 Jan 21.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy. Electronic address:

Autism spectrum disorder (ASD) is a heterogeneous condition linked to an anomalous neurodevelopment. Although the underlying causes of ASD are not well described, literature data strongly suggests a genetic component, with a complex inheritance pattern. It has recently been observed that CNVs (copy number variation) may play an important role in ASD manifestation and partially explain the complex heritability of this tract. Another factor That adds another level of complexity to ASD is its potential genetic heterogeneity. In this paper, we hypothesize that the different patterns of alteration within individuals with ASD may converge towards the same function. We genotyped a sample of 107 individuals through aCGH analysis for CNVs that were related (by localization) to approximately 1400 genes. The genes were tested for functional interactions and clustered in functional groups. We highlighted a functional genetic cluster of 256 genes potentially related to ASD. These altered genes may contribute to the same function, alterations of which increase the risk of ASD. After testing our functional cluster for biological functions, processes related to oxidative stress, immune system and energy metabolism are the pathways potentially involved with the biological alterations underlying ASD.
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http://dx.doi.org/10.1016/j.psychres.2021.113729DOI Listing
March 2021

Molecular Pathways within Autism Spectrum Disorder Endophenotypes.

J Mol Neurosci 2021 Jul 25;71(7):1357-1367. Epub 2021 Jan 25.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Torre Biologica Via C. Valeria-Gazzi, Messina, 98125, Italy.

Autism spectrum disorder (ASD) is a condition that includes a number of neurodevelopmental mental disorders. Recent genetic/genomic investigations have reported an increased prevalence of copy number variations (CNVs) in individuals with autism. Despite the extensive evidence of a genetic component, the genes involved are not known and the background is heterogeneous among subjects. As such, it is highly likely that multiple events (molecular cascades) are implicated in the development of autism. The aim of this work was to shed some light on the biological background behind this condition. We hypothesized that the heterogeneous alterations found within different individuals may converge into one or more specific biological functions (pathways) linked to the heterogeneous phenotypes commonly observed in subjects with ASD. We analyzed a sample of 107 individuals for CNV alterations and checked the genes located within the altered loci (1366). Then, we characterized the subjects for distinct phenotypes. After creating subsamples based on symptoms, the CNVs related to each specific symptom were used to create distinct networks associated with each phenotype (18 in total in the sample under analysis). These networks were independently clustered and enriched to identify potential common pathways involved in autism and variably combined with the clinical phenotype. The first 10 pathways of the analysis are discussed.
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http://dx.doi.org/10.1007/s12031-020-01782-7DOI Listing
July 2021

Correspondence on "Pathogenic variants in USP7 cause a neurodevelopmental disorder with speech delays, altered behavior, and neurologic anomalies" by Fountain et al.

Genet Med 2021 02 5;23(2):421-422. Epub 2020 Oct 5.

Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Messina, Italy.

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http://dx.doi.org/10.1038/s41436-020-00978-xDOI Listing
February 2021

Genetic analysis of the human insulin-like 3 gene in pediatric patients with testicular torsion.

Pediatr Surg Int 2018 Jul 21;34(7):807-812. Epub 2018 May 21.

Department of Human Pathology of Adult and Childhood "Gaetano Barresi", Unit of Pediatric Surgery, University of Messina, Via Consolare Valeria, 1, 98125, Messina, Italy.

Purpose: Testicular torsion (TT) mainly affects boys under 18 years old. To avoid orchiectomy, TT requires an immediate operative management. The etiology of TT is still controversial. Observed familiar recurrence suggests the presence of a genetic involvement. The INSL3 gene consists of two exons, and it is specifically expressed in fetal and adult Leydig cells. In transgenic mice, deletion of this gene was observed an increased testicular mobility and testicular torsion. We have hypothesized the possible involvement of the INSL3 gene as a predisposing factor of human TT.

Methods: We performed genetic analysis in 25 pediatric patients with unilateral and intravaginal TT (left, n = 13, 56%; right, n = 12, 48%). The age of the patients ranged from 1 to 16 years (median age n = 10.4 ± 5.46 years). In this study, we included two first male cousins affected by TT. Venous peripheral blood samples was obtained after parental written informed consent.

Results: The Thr60Ala polymorphism was detected in exon 1 of INSL3 gene and other 2 rarer variants (rs1047233 and rs1003887) were identified in the 3' untranslated region. These variants are prevalent in patients with TT instead of healthy subjects.

Conclusions: Additional studies in a larger population are needed to better understand the clinical consequence of the INSL 3 variations founded. This would allow in the future to identify the patients at risk of TT to improve clinical management.
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http://dx.doi.org/10.1007/s00383-018-4280-yDOI Listing
July 2018

FTL c.-168G>C Mutation in Hereditary Hyperferritinemia Cataract Syndrome: A New Italian Family.

Pediatr Dev Pathol 2018 Sep-Oct;21(5):456-460. Epub 2018 Feb 9.

1 Department of Human Pathology of Adult and Developmental Age "Gaetano Barresi", University Hospital of Messina, Messina, Italy.

We describe a new Italian family with 7 members affected by hereditary hyperferritinemia cataract syndrome (HHCS), an uncommon autosomal dominant disease caused by mutations of the iron-responsive element (IRE) of the ferritin light chain (FTL) gene determining its overexpression. The family diagnosis of HHCS took place after finding high ferritin levels in a 6-year-old girl. Seven members of the family had bilateral and symmetrical cataracts, normal iron, and hematological parameters except for high serum ferritin levels. About 160 families/unrelated cases with HHCS are known worldwide. This report documents a second Italian family, with a c.-168G>C mutation that is located in the highly conserved 3-nucleotide bulge structure of the FTL in the 5' untranslated region. This case shows how important the family history is in reaching a correct diagnosis and avoiding unnecessary and invasive analysis. HHCS should be considered in the differential diagnosis of childhood hyperferritinemia, especially in the presence of normal transferrin saturation.
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http://dx.doi.org/10.1177/1093526618755200DOI Listing
June 2019

A Novel Mutation of the δ-Globin Gene in an Asymptomatic 30-Year-Old Female.

Acta Haematol 2018;139(1):33-34. Epub 2018 Jan 13.

Department of Human Pathology, University Hospital, University of Messina, Messina, Italy.

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http://dx.doi.org/10.1159/000484973DOI Listing
March 2019

A child with severe iron-deficiency anemia and a complex TMPRSS6 genotype.

Hematology 2017 Oct 27;22(9):559-564. Epub 2017 Apr 27.

a Department of Human Pathology of Adult and Developmental Age 'Gaetano Barresi' , 'Gaetano Martino' University Hospital of Messina , Messina , Italy.

Objectives: We report a case of a 7-year-old girl with severe hypochromic microcytic anemia, who was unresponsive to classical iron supplements. We suspected IRIDA, iron-refractory iron-deficiency anemia, a genetic iron metabolism disorder, caused by TMPRSS6 variations. TMPRSS6 encodes matriptase-2, a negative regulator of hepcidin, and its pathological variants are related to normal to high levels of hepcidin. We analyzed the TMPRSS6 gene and we improved clinical management of the patient, selecting the appropriate supplementation therapy. Intervention & Technique: The parenteral iron therapy was started, but the patient was only partially responsive and the anemia persisted. To confirm the diagnosis, the TMPRSS6 gene sequence was analyzed by DNA sequencing and other relevant biochemical parameters were evaluated.

Results: The TMPRSS6 sequence analysis showed a complex genotype with a rare heterozygous missense variant, in addition to other common polymorphisms. The serum hepcidin value was normal. We unexpectedly observed a normalization of patient's hemoglobin (Hb) levels only after liposomal iron treatment.

Discussion And Conclusion: The proband was symptomatic for IRIDA during a critical phase of growth and development, but we did not find a clearly causative genotype. A long-term result, improving stably patient's Hb levels, was obtained only after liposomal iron supplementation. Children may be at greater risk for iron deficiency and the degree of anemia as well as the response to the iron supplements varies markedly patient to patient. Here, we show the importance of comprehensive study of these patients in order to collect useful information about genotype-phenotype association of genes involved in iron metabolism.
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http://dx.doi.org/10.1080/10245332.2017.1317990DOI Listing
October 2017