Alternative titles; symbols
DO: 0112283;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 16q23.3-q24.1 | ?Spondyloepiphyseal dysplasia, Kondo-Fu type | 618392 | Autosomal recessive | 3 | MBTPS1 | 603355 |
A number sign (#) is used with this entry because of evidence that the Kondo-Fu type of spondyloepiphyseal dysplasia (SEDKF) is caused by compound heterozygous mutation in the MBTPS1 gene (603355) on chromosome 16q23-q24. One such patient has been reported.
The Kondo-Fu type of spondyloepiphyseal dysplasia (SEDKF) is characterized by severely retarded growth and skeletal anomalies, including spondyloepiphyseal dysplasia with associated kyphosis and reduced bone mineral density. Elevated levels of blood lysosomal enzymes have also been observed (Kondo et al., 2018).
Kondo et al. (2018) studied an 11.5-year-old girl who showed severely retarded growth with skeletal anomalies, including a bone mineral density that was approximately 60% of that of healthy controls. She was small for gestational age at birth, with lengths and weights initially in the 5th centile, and after 6 months of age, growth in weight and height slowed down. At 2 years of age, bilateral cataracts were extracted, and at age 3.5 years, she underwent bilateral inguinal hernia repair. Although gross motor milestones were delayed, speech and cognitive development were normal. She showed limited response to growth hormone (GH1; 139250) replacement therapy, which was discontinued after 1 year. Evaluation at age 6 years for back pain showed short stature, pectus carinatum, kyphosis, and waddling gait; x-rays revealed spondyloepiphyseal dysplasia. At age 8, she was found to have markedly elevated plasma levels of various lysosomal enzymes, with normal urinary glycosaminoglycans. Bone mineral density was low at age 10, with DXA scan showing a z-score of -4.5 for total body less head and -3.3 for anterior-posterior spine. Echocardiogram at 10.5 years of age was normal. X-rays at 11.5 years of age showed stable complete anterolisthesis of vertebra L5 on S1, and bilateral shortening of the femoral necks with irregular and dysplastic appearance of the femoral and proximal tibial epiphyses. The fibulae were gracile, with valgus tibial bowing due to defective endochondral ossification. She also had brachydactyly and dysmorphic facial features, including prominent forehead and cheekbones and large posteriorly rotated ears. Her parents and 2 sisters were unaffected.
The transmission pattern of SEDKF in the patient reported by Kondo et al. (2018) was consistent with autosomal recessive inheritance.
In an 11.5-year-old girl with spondyloepiphyseal dysplasia and elevated plasma lysosomal enzymes, who was negative for mutation in mucolipidosis-associated genes, Kondo et al. (2018) performed whole-exome sequencing and identified compound heterozygosity for mutations in the MBTPS1 gene: a 1-bp duplication (603355.0001) and a missense mutation (D365G; 603355.0002). Her unaffected parents and sisters were each heterozygous for 1 of the mutations.
Kondo, Y., Fu, J., Wang, H., Hoover, C., McDaniel, J. M., Steet, R., Patra, D., Song, J., Pollard, L., Cathey, S., Yago, T., Wiley, G., and 12 others. Site-1 protease deficiency causes human skeletal dysplasia due to defective inter-organelle protein trafficking. JCI Insight 3: 121596, 2018. Note: Electronic Article. [PubMed: 30046013] [Full Text: https://doi.org/10.1172/jci.insight.121596]