@article {3535, title = {A neonate with a {\textquoteright}milky{\textquoteright} blood. What can it be?}, journal = {Arch Dis Child Fetal Neonatal Ed}, volume = {99}, year = {2014}, month = {2014 Nov}, pages = {F514}, keywords = {Female, Humans, Hyperlipoproteinemia Type IV, Infant, Newborn, Lipoprotein Lipase, Milk Proteins, Mutation}, issn = {1468-2052}, doi = {10.1136/archdischild-2014-305940}, author = {Bordugo, Andrea and Carlin, Eva and Demarini, Sergio and Faletra, Flavio and Colonna, Franco} } @article {3499, title = {Next generation sequencing in nonsyndromic intellectual disability: from a negative molecular karyotype to a possible causative mutation detection.}, journal = {Am J Med Genet A}, volume = {164A}, year = {2014}, month = {2014 Jan}, pages = {170-6}, abstract = {

The identification of causes underlying intellectual disability (ID) is one of the most demanding challenges for clinical Geneticists and Researchers. Despite molecular diagnostics improvements, the vast majority of patients still remain without genetic diagnosis. Here, we report the results obtained using Whole Exome and Target Sequencing on nine patients affected by isolated ID without pathological copy number variations, which were accurately selected from an initial cohort of 236 patients. Three patterns of inheritance were used to search for: (1) de novo, (2) X-linked, and (3) autosomal recessive variants. In three of the nine proband-parent trios analyzed, we identified and validated two de novo and one X-linked potentially causative mutations located in three ID-related genes. We proposed three genes as ID candidate, carrying one de novo and three X-linked mutations. Overall, this systematic proband-parent trio approach using next generation sequencing could explain a consistent percentage of patients with isolated ID, thus increasing our knowledge on the molecular bases of this disease and opening new perspectives for a better diagnosis, counseling, and treatment.

}, keywords = {Computational Biology, Exome, Female, Genes, Recessive, Genes, X-Linked, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Intellectual Disability, Karyotype, Male, Mutation, Workflow}, issn = {1552-4833}, doi = {10.1002/ajmg.a.36274}, author = {Athanasakis, Emmanouil and Licastro, Danilo and Faletra, Flavio and Fabretto, Antonella and Dipresa, Savina and Vozzi, Diego and Morgan, Anna and d{\textquoteright}Adamo, Adamo P and Pecile, Vanna and Biarn{\'e}s, Xevi and Gasparini, Paolo} } @article {3529, title = {A novel deletion mutation involving TMEM38B in a patient with autosomal recessive osteogenesis imperfecta.}, journal = {Gene}, volume = {545}, year = {2014}, month = {2014 Jul 25}, pages = {290-2}, abstract = {

Osteogenesis imperfecta (OI) is a hereditary bone disease characterized by decreased bone density and multiple fractures, usually inherited in an autosomal dominant manner. Several gene encoding proteins related to collagen metabolism have been described in some cases of autosomal recessive OI (including CRTAP, LEPRE1, PPIB, FKBP65, SERPINF1, BMP1, WNT1, FKBP10). Recently, TMEM38B, a gene that encodes TRIC-B, a monovalent cation-specific channel involved in calcium flux from intracellular stores and in cell differentiation, has been associated with autosomal recessive OI. Here, we describe the second deletion-mutation involving the TMEM38B gene in an 11 year-old Albanian female with a clinical phenotype of OI, born to parents with suspected consanguinity. SNP array analysis revealed a homozygous region larger than 2 Mb that overlapped with the TMEM38B locus and was characterized by a 35 kb homozygous deletion involving exons 1 and 2 of TMEM38B gene.

}, keywords = {Child, Chromosomes, Human, Pair 19, DNA Mutational Analysis, Exons, Female, Genes, Recessive, Homozygote, Humans, Ion Channels, Osteogenesis Imperfecta, Sequence Deletion}, issn = {1879-0038}, doi = {10.1016/j.gene.2014.05.028}, author = {Rubinato, Elisa and Morgan, Anna and D{\textquoteright}Eustacchio, Angela and Pecile, Vanna and Gortani, Giulia and Gasparini, Paolo and Faletra, Flavio} } @article {3477, title = {A novel P2RX2 mutation in an Italian family affected by autosomal dominant nonsyndromic hearing loss.}, journal = {Gene}, volume = {534}, year = {2014}, month = {2014 Jan 25}, pages = {236-9}, abstract = {

Hereditary hearing loss (HHL) is a common disorder accounting for at least 60\% of prelingual deafness. It is characterized by a large genetic heterogeneity, and despite the presence of a major gene, still there is a need to search for new causative mutations/genes. Very recently, a mutation within ATP-gated P2X(2) receptor (ligand-gated ion channel, purinergic receptor 2) gene (P2RX2) at DNFA41 locus has been reported leading to a bilateral and symmetrical sensorineural non-syndromic autosomal dominant HHL in two Chinese families. We performed a linkage analysis in a large Italian family with a dominant pattern of inheritance showing a significant 3.31 LOD score in a 2Mb region overlapping with the DNFA41 locus. Molecular analyses of P2RX2 identified a novel missense mutation (p.Gly353Arg) affecting a residue highly conserved across species. Visual inspection of the protein structure as obtained from comparative modeling suggests that substitution of the small glycine residue with a charged bulky residue such as an arginine that is close to the {\textquoteright}neck{\textquoteright} of the region responsible for ion channel gating should have a high energetic cost and should lead to a severely destabilization of the fold. The identification of a second most likely causative mutation in P2RX2 gene further supports the possible role of this gene in causing autosomal dominant HHL.

}, keywords = {Amino Acid Sequence, Deafness, European Continental Ancestry Group, Female, Genotype, Hearing Loss, Sensorineural, Humans, Italy, Male, Molecular Sequence Data, Mutation, Missense, Pedigree, Receptors, Purinergic P2X2}, issn = {1879-0038}, doi = {10.1016/j.gene.2013.10.052}, author = {Faletra, Flavio and Girotto, Giorgia and d{\textquoteright}Adamo, Adamo Pio and Vozzi, Diego and Morgan, Anna and Gasparini, Paolo} } @article {1956, title = {A novel CRYBB2 missense mutation causing congenital autosomal dominant cataract in an Italian family.}, journal = {Ophthalmic Genet}, volume = {34}, year = {2013}, month = {2013 Mar-Jun}, pages = {115-7}, abstract = {

Congenital cataract is a leading cause of visual impairment in children and brings approximately 10\% of childhood blindness worldwide. Molecular analysis revealed ~60 loci to be associated with several phenotypes of childhood cataracts. Until now, more than 30 loci and 18 genes on different chromosomes have been associated with autosomal dominant congenital cataract (ADCC). Here, we present a three-generation Italian family with a non syndromic ADCC. A linkage analysis carried out using HumanCytoSNP-12 DNA Analysis BeadChip led us to identify ten genomic regions virtually involved in the disease. All the genes located in these regions were scored for possible relationship with ADCC and, according to a strict clinical and genetic selection, 4 genes have been analyzed. A novel sequence variant was found in the CRYBB2 gene (p.Ser143Phe). This variant affects a conserved aminoacid in the third Greek key motif of the protein, cosegregates with the disease phenotype in all affected individuals and is not present both in the unaffected family members and 100 healthy control subjects. Finally, we identified the first CRYBB2 mutation in an Italian family causing a clinical picture of ADCC.

}, keywords = {Amino Acid Sequence, beta-Crystallin B Chain, Cataract, DNA Mutational Analysis, Female, Genes, Dominant, Genetic Linkage, Genotype, Humans, Italy, Male, Molecular Sequence Data, Mutation, Missense, Pedigree, Phenotype}, issn = {1744-5094}, doi = {10.3109/13816810.2012.707273}, author = {Faletra, Flavio and d{\textquoteright}Adamo, Adamo Pio and Pensiero, Stefano and Athanasakis, Emmanouil and Catalano, Dario and Bruno, Irene and Gasparini, Paolo} } @article {1662, title = {A new case of duplication of the MDS region identified by high-density SNP arrays and a review of the literature.}, journal = {J Appl Genet}, volume = {52}, year = {2011}, month = {2011 Feb}, pages = {77-80}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Child, Female, Gene Duplication, Humans, Microtubule-Associated Proteins, Myelodysplastic Syndromes, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Prognosis}, issn = {2190-3883}, doi = {10.1007/s13353-010-0004-2}, author = {Faletra, Flavio and Devescovi, Raffaella and Pecile, Vanna and Fabretto, Antonella and Carrozzi, Marco and Gasparini, Paolo} }