Elsa Lucas-Castro, Francisca Diaz-González, Silvia Modamio-Høybjor, Manuel Parrón-Pajares, Sonia Pajares, Laura Gort, Julián Nevado, Pablo Lapunzina, Antonio Leiva-Gea, Karen E Heath
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Novel MBTPS1 Variants and Cutis Laxa Phenotype in the 8th Reported Case of Spondyloepiphyseal Dysplasia, Kondo-Fu Type.
Spondyloepiphyseal dysplasia, Kondo-Fu (SEDKF) type is a rare skeletal dysplasia caused by biallelic variants in MBTPS1. To date, only seven SEDKF cases have been reported in the literature. Here, we report the eighth, a 20-year-old male presenting with severe disproportionate short stature, spondyloepiphyseal dysplasia, and the previously unreported feature of cutis laxa, which led to the clinical suspicion of geroderma osteodysplasica. Whole exome sequencing identified compound heterozygosity for a predicted splicing variant and a complete gene deletion in the patient. Functional validation using RNA splicing assays confirmed aberrant splicing, establishing the molecular diagnosis of SEDKF. This case broadens the clinical and molecular spectrum of MBTPS1-related disorders by presenting a novel combination of variants and phenotypic features.
期刊介绍:
Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice.
Topics of particular interest are:
• Linking genetic variations to disease
• Genome rearrangements and disease
• Epigenetics and disease
• The translation of genotype to phenotype
• Genetics of complex disease
• Management/intervention of genetic diseases
• Novel therapies for genetic diseases
• Developmental biology, as it relates to clinical genetics
• Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease