ABSTRACT
The skeletal ciliopathies are a heterogeneous group of disorders with a significant clinical and genetic variability and the main clinical features are thoracic hypoplasia and short tubular bones. To date, 25 genes have been identified in association with skeletal ciliopathies. Mutations in the KIAA0753 gene have recently been associated with Joubert syndrome (JBTS) and orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants in KIAA0753 in four patients with short-rib type skeletal dysplasia. The manifestations in our patients are variable and ranging from fetal lethal to viable and moderate skeletal dysplasia with narrow thorax and abnormal metaphyses. We demonstrate that KIAA0753 is expressed in normal fetal human growth plate and show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by our findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning.
Subject(s)
Ciliopathies/genetics , Genetic Predisposition to Disease , Microtubule-Associated Proteins/genetics , Muscle, Skeletal , Abnormalities, Multiple/genetics , Abnormalities, Multiple/physiopathology , Cerebellum/abnormalities , Cerebellum/physiopathology , Child , Child, Preschool , Ciliopathies/physiopathology , Eye Abnormalities/genetics , Eye Abnormalities/physiopathology , Female , Homozygote , Humans , Infant , Kidney Diseases, Cystic/genetics , Kidney Diseases, Cystic/physiopathology , Male , Muscle, Skeletal/abnormalities , Mutation , Orofaciodigital Syndromes/genetics , Orofaciodigital Syndromes/physiopathology , Pedigree , Phenotype , Retina/abnormalities , Retina/physiopathologyABSTRACT
Inherited ataxias are an extremely heterogeneous group of disorders. Autosomal recessive spinocerebellar ataxia 20 (SCAR20) is a recently described disorder characterized by intellectual disability, ataxia, coarse facial features, progressive loss of Purkinje cells in the cerebellum and often hearing loss and skeletal abnormalities. Mutations in the gene SNX14, which plays an important role in autophagy, have been found to cause SCAR20. The unique clinical findings of progressive coarsening of facial features makes the clinical phenotype recognizable among the various hereditary ataxias. Here we report on a child with a novel missense mutation in the SNX14 gene that appears to be debilitating for protein conformation, function and review the previously reported cases from 15 families.
Subject(s)
Cerebellum/physiopathology , Purkinje Cells/pathology , Sorting Nexins/genetics , Spinocerebellar Ataxias/genetics , Autophagy/genetics , Child , Female , Humans , Mutation , Pedigree , Phenotype , Spinocerebellar Ataxias/physiopathologyABSTRACT
Smut caused by Sporisorium scitamineum is one of the important diseases of sugarcane with global significance. Despite the intriguing nature of sugarcane, S. scitamineum interaction, several pertinent aspects remain unexplored. This study investigates the proteome level alterations occurring in the meristem of a S. scitamineum infected susceptible sugarcane cultivar at whip emergence stage. Differentially abundant proteins were identified by 2DE coupled with MALDI-TOF/TOF-MS. Comprehensively, 53 sugarcane proteins identified were related to defence, stress, metabolism, protein folding, energy, and cell division; in addition, a putative effector of S. scitamineum, chorismate mutase, was identified. Transcript expression vis-à-vis the activity of phenylalanine ammonia lyase was relatively higher in the infected meristem. Abundance of seven candidate proteins in 2D gel profiles was in correlation with its corresponding transcript expression levels as validated by qRT-PCR. Furthermore, this study has opened up new perspectives on the interaction between sugarcane and S. scitamineum.
