Exome Sequencing Reveals Biallelic Mutations inGene in a Girl with a Very Rare Skeletal Dysplasia.
Source: PubMed, NCBI / U.S. National Library of Medicine
The Kondo-Fu type of spondyloepiphyseal dysplasia (SEDKF) is a rare skeletal dysplasia caused by homozygous or compound heterozygous mutations in thegene. Thegene encodes a protein that is involved in the regulation of cholesterol and fatty acid metabolism. Mutations incan lead to reduced levels of these lipids, which can have a number of effects on development, including skeletal anomalies, growth retardation, and elevated levels of blood lysosomal enzymes. This work reports the case of a 5-year-old girl with SEDKF. The patient had a severely short stature and a number of skeletal anomalies, including kyphosis, pectus carinatum, and reduced bone mineral density. She also had early onset cataracts and inguinal hernias. Genetic testing revealed two novel compound heterozygous variants in thegene. These variants are predicted to disrupt the function of the MBTPS1 protein, which is consistent with the patient's clinical presentation. This case report adds to the growing body of evidence that mutations in thegene are causal of SEDKF. We summarized the features of previous reported cases (with age ranges from 4 to 24 years) and identified that 80% had low stature, 70% low weight, 80% had bilateral cataracts and 70% showed Spondyloepiphyseal dysplasia on X-rays. The findings of this study suggest that SEDKF is a clinically heterogeneous disorder that can present with a variety of features. Further studies are needed to better understand the underlying mechanisms of SEDKF and to dev
Abstract
The Kondo-Fu type of spondyloepiphyseal dysplasia (SEDKF) is a rare skeletal dysplasia caused by homozygous or compound heterozygous mutations in thegene. Thegene encodes a protein that is involved in the regulation of cholesterol and fatty acid metabolism. Mutations incan lead to reduced levels of these lipids, which can have a number of effects on development, including skeletal anomalies, growth retardation, and elevated levels of blood lysosomal enzymes. This work reports the case of a 5-year-old girl with SEDKF. The patient had a severely short stature and a number of skeletal anomalies, including kyphosis, pectus carinatum, and reduced bone mineral density. She also had early onset cataracts and inguinal hernias. Genetic testing revealed two novel compound heterozygous variants in thegene. These variants are predicted to disrupt the function of the MBTPS1 protein, which is consistent with the patient's clinical presentation. This case report adds to the growing body of evidence that mutations in thegene are causal of SEDKF. We summarized the features of previous reported cases (with age ranges from 4 to 24 years) and identified that 80% had low stature, 70% low weight, 80% had bilateral cataracts and 70% showed Spondyloepiphyseal dysplasia on X-rays. The findings of this study suggest that SEDKF is a clinically heterogeneous disorder that can present with a variety of features. Further studies are needed to better understand the underlying mechanisms of SEDKF and to develop more effective treatments.