Subject(s)
Abnormalities, Multiple/genetics , Eyelids/abnormalities , Adult , Cleft Lip/genetics , Cleft Palate/genetics , DNA-Binding Proteins/genetics , Ectodermal Dysplasia/genetics , Female , Humans , Infant, Newborn , Male , Point Mutation , Syndrome , Trans-Activators/genetics , Transcription Factors , Tumor Suppressor Proteins/geneticsABSTRACT
BACKGROUND: Familial tumoral calcinosis (FTC) is a rare autosomal recessive disease characterised by the development of multiple calcified masses in periarticular soft tissues; GALNT3 gene mutations have recently been described in an African American and in a Druse Arab family with FTC. OBJECTIVE: To report the clinical and histological features caused by a new GALNT3 mutation in a white family. RESULTS: Homozygosity for the nonsense mutation Lys463X was found in both affected siblings, who displayed a classic phenotype, the male also having testicular microlithiasis. He is the first subject described with testicular microlithiasis in FTC. CONCLUSIONS: The high testicular expression of GALNT3 suggests that the gene alteration could act locally by causing deposition of calcium, and the testis may be an underestimated site of calcification in FTC. Autoimmune diseases are present in several members of the family. Although immune disorders have been described in FTC, autoimmunity does not segregate with the GALNT3 mutation in this family.
Subject(s)
Calcinosis/genetics , Codon, Nonsense , Lithiasis/genetics , N-Acetylgalactosaminyltransferases/genetics , Neoplasm Proteins/genetics , Testicular Diseases/genetics , Autoimmune Diseases/genetics , Autoimmune Diseases/metabolism , Calcinosis/metabolism , Calcinosis/pathology , Child , Humans , Italy , Lithiasis/metabolism , Lithiasis/pathology , Male , Pedigree , Testicular Diseases/ethnology , Testicular Diseases/metabolism , White People , Polypeptide N-acetylgalactosaminyltransferaseSubject(s)
Cleft Lip/genetics , Cleft Palate/genetics , Ectodermal Dysplasia/genetics , Frameshift Mutation , Phosphoproteins/genetics , Trans-Activators/genetics , Base Sequence , Cleft Lip/diagnosis , Cleft Palate/diagnosis , DNA Mutational Analysis , DNA-Binding Proteins , Ectodermal Dysplasia/diagnosis , Female , Genes, Tumor Suppressor , Genetic Predisposition to Disease , Humans , Hypohidrosis/diagnosis , Hypohidrosis/genetics , Male , Pedigree , Syndrome , Transcription Factors , Tumor Suppressor ProteinsABSTRACT
Diamond-Blackfan anemia (DBA) is a congenital disease characterized by defective erythroid progenitor maturation and physical malformations. Most cases are sporadic, but dominant or, more rarely, recessive inheritance is observed in 10% of patients. Mutations in the gene encoding ribosomal protein (RP) S19 have recently been found in 25% of patients with either the dominant or the sporadic form. DBA is the first human disease due to mutations in a ribosomal structural protein. Families unlinked to this locus have also been reported. In an investigation of 23 individuals, we identified eight different mutations in 9 patients. These include five missense, one frameshift, one splice site defect, and one 4-bp insertion in the regulatory sequence. Seven mutations are new; one has so far been found in 8 patients and is a relatively common de novo event. Two mutations are predicted to generate a truncated protein. We also report the prevalence of RPS 19 mutations in the Italian DBA population, as shown by an analysis of 56 patients. No genotype-phenotype correlation was found between patients with the same mutation. The main clinical applications for molecular analysis are clinical diagnosis of patients with an incomplete form of DBA and testing of siblings of a patient with a severe form so as to avoid using those who carry a mutation and a silent phenotype as allogeneic stem cell donors.
