@article {1954, title = {Identification of a New Mutation (L46P) in the Human NOG Gene in an Italian Patient with Symphalangism Syndrome.}, journal = {Mol Syndromol}, volume = {3}, year = {2012}, month = {2012 Jun}, pages = {21-24}, abstract = {

Proximal symphalangism (SYM1) is a joint morphogenesis disorder characterized by stapes ankylosis, proximal interphalangeal joint fusion, skeletal anomalies and conductive hearing loss. Noggin is a bone morphogenetic protein (BMP) antagonist essential for normal bone and joint development in humans and mice. Autosomal dominant mutations have been described in the NOG gene, encoding the noggin protein. We analyzed an Italian sporadic patient with SYM1 due to a novel NOG mutation (L46P) based on a c.137T>C transition. A different pathogenic mutation in the same codon (L46D) has been previously described in an in vivo chicken model. An in silico model shows a decreased binding affinity between noggin and BMP7 for both L46D and L46P compared to the wild type. Therefore, this codon should play an important role in BMP7 binding activity of the noggin protein and consequently to the joint morphogenesis.

}, issn = {1661-8769}, doi = {000337928}, author = {Athanasakis, E and Biarn{\'e}s, X and Bonati, M T and Gasparini, P and Faletra, F} } @article {1953, title = {Two Novel COH1 Mutations in an Italian Patient with Cohen Syndrome.}, journal = {Mol Syndromol}, volume = {3}, year = {2012}, month = {2012 Jun}, pages = {30-33}, abstract = {

Cohen syndrome (CS) is an autosomal recessive disease caused by mutations in the COH1 gene. It is characterized by intellectual disability, hypotonia, joint hyperlaxity, severe myopia, characteristic facial dysmorphisms and, in some cases, intermittent isolated neutropenia. We investigated an Italian patient with CS together with his family. Genetic analysis disclosed 2 novel mutations: the first is an intronic mutation (c.8697-9A>G) creating a new splice site 8 nucleotides upstream, and the second is a duplication of 1 base (c.10156dupA) generating a premature stop codon. The compound heterozygous mutations explain the proband{\textquoteright}s phenotype and improved the knowledge of genotype-phenotype correlation.

}, issn = {1661-8769}, doi = {000338816}, author = {Athanasakis, E and Fabretto, A and Faletra, F and Mocenigo, M and Morgan, A and Gasparini, P} } @article {1702, title = {Analysis of DEFB1 regulatory SNPs in cystic fibrosis patients from North-Eastern Italy.}, journal = {Int J Immunogenet}, volume = {37}, year = {2010}, month = {2010 Jun}, pages = {169-75}, abstract = {

Cystic fibrosis (CF) transmembrane regulator protein (CFTR) gene is undoubtedly the main genetic factor involved in the modulation of CF phenotype. However, other factors such as human defensins and the genes encoding for these antimicrobial peptides have been hypothesized as possible modifiers influencing airways infection in CF patients, but their role in the pathogenesis of lung disease is still debated. Since DEFB1 gene encoding for human beta-defensin 1 displays features such as antimicrobial or chemotactic activity playing a role in inflammation, it has been considered as a possible candidate CF modifier gene. We analysed three single nucleotide polymorphisms (SNPs) in the 5{\textquoteright}-untranslated region of the DEFB1 gene (namely g-52G>A, g-44C>G and g-20G>A) in a group of 62 CF patients from North Eastern Italy, and in 130 healthy controls, with the aim of verifying the possible association of these functional SNPs with the pulmonary phenotype of CF patients. DEFB1 SNPs have been genotyped by using Taqman allele-specific fluorescent probes and a real-time PCR platform. No significant differences were found for allele, genotype and haplotype frequencies of DEFB1 g-52G>A, g-44C>G and g-20G>A SNPs in CF patients stratified for Pseudomonas aeruginosa infection, as well as in patients with a severe and mild clinical phenotype or in patients stratified for CFTR genotypes. DEFB1 allele, genotype and haplotype frequencies of CF patients globally considered were similar to those of healthy controls. Our findings are discordant with respect to another recent study performed on CF patients coming from Southern Italy, probably due to different ethnicity of the patients.

}, keywords = {5{\textquoteright} Untranslated Regions, Adolescent, Alleles, beta-Defensins, Case-Control Studies, Child, Child, Preschool, Chronic Disease, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Female, Gene Frequency, Genotype, Haplotypes, Humans, Immunity, Innate, Infant, Infant, Newborn, Italy, Male, Polymorphism, Single Nucleotide, Pseudomonas Infections}, issn = {1744-313X}, doi = {10.1111/j.1744-313X.2010.00907.x}, author = {Segat, L and Morgutti, M and Athanasakis, E and Trevisiol, C and Amaddeo, A and Poli, F and Crovella, S} }