Exome Sequencing Reveals Biallelic Mutations in MBTPS1 Gene in a Girl with a Very Rare Skeletal Dysplasia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sample Extraction and Sequencing
2.2. Bioinformatics Pipeline, Variant Detection and Interpretation
3. Results
3.1. Case Report
3.2. Bioinformatic Analysis Revealed Pathogenic Compound Heterozygous Mutation in MBTPS1 Gene
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Yuji Kondo et al., 2018 [1] | Schweitzer et al., 2019 [20] | Meyer et al., 2020 [2] | Carvalho et al., 2020 [13] | Chen et al., 2022 (Patient 1) [21] | Chen et al., 2022 (Patient 2) [21] | Alotaibi et al., 2022 [12] | Yuan et al., 2022 [11] | Chen et al., 2023 [22] | Our Case | YES % | |
---|---|---|---|---|---|---|---|---|---|---|---|
PMID: 30046013 | PMID: 31070020 | PMID: 32857899 | PMID: 32420688 | PMID: 35362222 | PMID: 35362222 | PMID: 36330313 | PMID: 36714646 | PMID: 36816387 | NA | ||
Sex | F | F | M | F | M | F | F | M | M | F | 60 (F) |
Age (years) | 8 | 24 | 7 | 5 | 14 | 5 | 10 | 12 | 6 | 4 | |
Small for gestational age | Yes | No | Yes | Yes | NA | NA | Yes | No | No | Yes | 50 |
Short stature | Yes | No | Yes | Yes | Yes | No | Yes | Yes | Yes | Yes | 80 |
Low weight | Yes | No | Yes | Yes | NA | NA | Yes | Yes | Yes | Yes | 70 |
Spondyloepiphyseal dysplasia on X-ray | Yes | NA | No | Yes | Yes | No | Yes | Yes | Yes | Yes | 70 |
Prominent forehead | Yes | No | No | Yes | No | No | Yes | No | Yes | Yes | 50 |
Micrognathia | No | No | No | Yes | No | No | Yes | Yes | Yes | Yes | 50 |
Large and/or dysplastic ears | Yes | No | Yes | Yes | No | No | Yes | Yes | Yes | Yes | 70 |
Bilateral cataracts, early onset | Yes (2 yo) | No | Yes (adolescence) | Yes (10 mo) | Yes (?) | Yes (?) | No | Yes (2 yo) | Yes (2 yo) | Yes (2 yo) | 80 |
Pectus carinatum | Yes | No | No | Yes | NA | NA | Yes (mild) | Yes | No | Yes | 50 |
Pectus excavatum | No | No | No | No | NA | NA | No | No | Yes | No | 10 |
Inguinal hernias | Yes | No | Yes | No | No | No | No | Yes | No | Yes | 40 |
Low bone mineral density | No | No | No | Yes (radiography) | NA | NA | Yes | Yes (radiography) | Yes (radiography) | Not assessed | 40 |
Anterolisthesis of L5 on S1 | Yes | No | No | No | No | No | No | No | No | Yes | 20 |
Kypho-scoliosis | Yes | No | No | Yes | NA | NA | Yes | Yes (mild) | Yes | No | 50 |
Chronic back pain | Yes | No | No | No | No | No | No | No | No | Yes | 20 |
Bilateral shortening of femoral necks | Yes | No | No | Yes | NA | NA | No | No | No | Yes | 30 |
Irregular and dysplastic appearance of femoral epiphyses | Yes | No | No | Yes | NA | NA | Yes | Yes | No | Yes | 50 |
Irregular and dysplastic appearance of proximal tibial epiphyses | Yes | No | No | Yes | NA | NA | No | No | No | No | 20 |
Gracile fibulae | Yes | No | No | No | NA | NA | Yes | No | No | No | 20 |
Valgus bowing of tibiae | Yes | No | No | No | NA | NA | Yes | No | No | No | 20 |
Defective endochondral ossification | Yes | No | No | No | NA | NA | No | No | No | No | 10 |
Delayed ossification of epiphyses | No | No | No | No | NA | NA | No | No | No | No | 0 |
Delayed ossification of carpal bones | No | No | No | No | NA | NA | No | No | Yes | Not assessed | 10 |
Brachydactyly | No | No | No | No | NA | NA | Yes | No | No | Yes | 20 |
Shortening of tubular bones | No | No | No | Yes | NA | NA | Yes | No | No | Yes | 30 |
Delayed gross motor milestones | Yes | No | No | Yes | No | Yes | Yes | No | No | No | 40 |
Elevated lysosomal enzymes | Yes | No | Yes | Yes | No | No | Yes | Not assessed | Not assessed | Not assessed | 40 |
HyperCKemia | No | Yes | No | No | No | No | No | No | No | No | 10 |
Focal myoedema | No | Yes | No | No | No | No | No | No | No | No | 10 |
Cutaneous lesions | No | No | No | No | Yes (psoriasis, ichthyosis) | Yes (psoriasis, ichthyosis) | No | No | No | No | 20 |
Mucosal lesions | No | No | No | No | Yes | No | No | No | No | No | 10 |
Sparse hair | No | No | No | No | Yes | Yes | No | No | No | Yes | 30 |
Consanguinity | No | Not assessed | Yes (distantly related) | Yes (second degree cousins) | No | No | Yes (cousins) | No | No | No | 30 |
Associated genetic variant(s) (NM_003791.3) | c.285dupT, p.(Asp96X)/c.1094A-G, p.(Asp365Gly) | c.3007C>T, p.(Pro1003Ser) | c.1094A>G, p.(Asp365Gly) | c.2948G>A, p.(Trp983ter) | c.1064T>G, p.(Val355Gly)/c.3157T>C, p.(Ter1053Arg) | c.2072-2A>T, p.(Ter1053Cys) | c.2634C>A, p.(Ser878Arg) | c.2656C>T, p.(Q886 *)/c.774C>T, p.(A258=) | c.1589A>G, p.(Asp530Gly)/c.163T > C, p.(Glu55Lys) | c.2355delG, p.(Met785fs)/c.1094A>G, p.(Asp365Gly) | |
Zigocity/inheritance | compound heterozygous | heterozygous, de novo | Homozygous | Homozygous | compound heterozygous | compound heterozygous | Homozygous | compound heterozygous | compound heterozygous | compound heterozygous | |
Splicing, frameshift or stop codon | 2 | 0 | 0 | 2 | 1 | 2 | 0 | 2 | 0 | 1 | |
Missense | 0 | 1 | 2 | 0 | 1 | 0 | 2 | 0 | 2 | 1 | |
Functional studies on variants | Yes | Yes | No | No | Yes | Yes | No | Yes | No | No | |
Initially Misdiagnosed as Silver–Russell syndrome | Yes | No | Yes | No | No | No | No | No | No | Yes | 30 |
Final Diagnosis | SEDKF | complex phenotype | SEDKF | SEDKF | CAOP | CAOP | SEDKF | SEDKF | SEDKF | SEDKF |
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Raggio, V.; Rodríguez, S.; Feder, S.; Gueçaimburú, R.; Spangenberg, L. Exome Sequencing Reveals Biallelic Mutations in MBTPS1 Gene in a Girl with a Very Rare Skeletal Dysplasia. Diagnostics 2024, 14, 313. https://doi.org/10.3390/diagnostics14030313
Raggio V, Rodríguez S, Feder S, Gueçaimburú R, Spangenberg L. Exome Sequencing Reveals Biallelic Mutations in MBTPS1 Gene in a Girl with a Very Rare Skeletal Dysplasia. Diagnostics. 2024; 14(3):313. https://doi.org/10.3390/diagnostics14030313
Chicago/Turabian StyleRaggio, Víctor, Soledad Rodríguez, Sandra Feder, Rosario Gueçaimburú, and Lucía Spangenberg. 2024. "Exome Sequencing Reveals Biallelic Mutations in MBTPS1 Gene in a Girl with a Very Rare Skeletal Dysplasia" Diagnostics 14, no. 3: 313. https://doi.org/10.3390/diagnostics14030313