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Spondyloepimetaphyseal Dysplasia Bieganski Type

1. Disease Information

2026-05-08
Falcon MONDO:0010275 Model: Edison Scientific Literature 23 citations

1. Disease Information

1.1 Overview

SEMD-BT is an ultra-rare Mendelian skeletal dysplasia historically defined by radiographic involvement of the spine (spondylo-), epiphyses (epimetaphyseal/epiphyseal), and metaphyses, with short stature and variable extraskeletal features. In modern molecular literature, “Bieganski type” is most consistently tied to a severe X-linked disorder with hypomyelinating leukodystrophy/neurodegeneration and a skeletal dysplasia phenotype (AIFM1), while a separate autosomal recessive SEMD/SED phenotype with elevated plasma lysosomal enzymes is caused by MBTPS1. (mierzewska2017spondyloepimetaphysealdysplasiawith pages 1-2, edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 1-4, edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 8-11, carvalho2020spondyloepimetaphysealdysplasiawith pages 1-3, kondo2018site1proteasedeficiency pages 1-2)

1.2 Key identifiers

ICD-10/ICD-11, MeSH, and Orphanet identifiers were not retrievable from the currently available evidence corpus in this run; therefore, they are not asserted here.

1.3 Common synonyms / alternative names (as used in sources)

1.4 Evidence sources

Most information is from aggregated disease-level literature (case reports/series and reviews), not EHR-derived cohort studies. (edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 1-4, carvalho2020spondyloepimetaphysealdysplasiawith pages 1-3, kondo2018site1proteasedeficiency pages 1-2)

2. Etiology

2.1 Disease causal factors (genetic)

Two primary genetic etiologies appear in the literature under overlapping SEMD terminology:

(A) AIFM1-related X-linked SEMD with cerebral hypomyelination/neurodegeneration

  • Gene: AIFM1 (apoptosis-inducing factor mitochondria-associated 1). (mierzewska2017spondyloepimetaphysealdysplasiawith pages 1-2, edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 1-4)
  • Inheritance: X-linked recessive (male predominance, no male-to-male transmission). (temtamy2007geneticheterogeneityin pages 18-20)
  • Abstract quote (supporting definition and gene-region mechanism): “Spondylometaphyseal dysplasia with cerebral hypomyelination (SMD‐H) is a very rare but distinctive phenotype, unusually combining spondylometaphyseal dysplasia with hypomyelinating leukodystrophy. Recently, SMD‐H has been associated with variants confined to a specific intra‐genic locus involving Exon 7…”. (American Journal of Medical Genetics Part A; Jan 2021; https://doi.org/10.1002/ajmg.a.62072) (edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 1-4)

(B) MBTPS1-related autosomal recessive SEMD/SED with elevated plasma lysosomal enzymes (SED Kondo–Fu type)

2.2 Risk factors / protective factors / gene–environment interactions

For both entities, the available evidence supports monogenic causation and does not identify validated environmental risk factors, protective factors, or gene–environment interactions beyond standard Mendelian recurrence risks. (temtamy2007geneticheterogeneityin pages 18-20, kondo2018site1proteasedeficiency pages 1-2)

3. Phenotypes (clinical and radiographic)

3.1 AIFM1-associated X-linked SEMD with hypomyelination (SMD-H)

Phenotype types: developmental/neurologic signs, skeletal dysplasia, characteristic neuroimaging.

Key reported phenotypes (with suggested HPO terms): - Hypomyelinating leukodystrophy / delayed myelination (HP:0003432 Abnormal myelination; HP:0002188 Hypomyelination). (edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 1-4, temtamy2007geneticheterogeneityin pages 18-20) - Progressive neurodegeneration involving CNS/PNS (HP:0002344 Progressive neurologic deterioration; HP:0003324 Generalized hypotonia; HP:0001263 Global developmental delay). (mierzewska2017spondyloepimetaphysealdysplasiawith pages 1-2, edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 1-4) - Microcephaly (HP:0000252 Microcephaly) and intellectual disability (HP:0001249 Intellectual disability) noted in historical descriptions. (temtamy2007geneticheterogeneityin pages 18-20) - Skeletal dysplasia involving spine/metaphyses/epiphyses (HP:0002650 Spondyloepimetaphyseal dysplasia; HP:0000925 Abnormality of the vertebral column; HP:0002758 Abnormal metaphysis morphology; HP:0002657 Abnormal epiphysis morphology). (mierzewska2017spondyloepimetaphysealdysplasiawith pages 1-2, edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 8-11, temtamy2007geneticheterogeneityin pages 18-20) - Kyphoscoliosis / thoracolumbar deformity (HP:0002751 Kyphoscoliosis; HP:0005619 Thoracolumbar kyphosis) and joint contractures (HP:0001371 Flexion contracture). (mierzewska2017spondyloepimetaphysealdysplasiawith pages 1-2, edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 8-11, temtamy2007geneticheterogeneityin pages 18-20)

Temporal pattern: onset around infancy with progressive neurologic decline; skeletal findings may be more apparent later in childhood. (mierzewska2017spondyloepimetaphysealdysplasiawith pages 1-2, edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 1-4)

Radiographic and imaging descriptors (examples): “irregular, flared and cupped metaphyses with metaphyseal striations,” small irregular epiphyses, platyspondyly/hyperkyphosis, and brain MRI “diffuse supratentorial hypomyelination”. (edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 8-11)

3.2 MBTPS1-associated SEDKF / SEMD with elevated plasma lysosomal enzymes

Phenotype types: disproportionate growth failure, ophthalmologic findings, skeletal radiographic findings, and characteristic laboratory abnormalities.

Key phenotypes (with suggested HPO terms): - Severe short stature / growth retardation (HP:0004322 Short stature). (raggio2024exomesequencingreveals pages 1-2, carvalho2020spondyloepimetaphysealdysplasiawith pages 1-3, raggio2024exomesequencingreveals pages 2-4) - Early-onset cataracts (HP:0000518 Cataract). (carvalho2020spondyloepimetaphysealdysplasiawith pages 1-3, liaqat2024acaseof pages 1-2, raggio2024exomesequencingreveals pages 2-4) - Spondyloepiphyseal/epimetaphyseal dysplasia on X-ray (HP:0002650 Spondyloepimetaphyseal dysplasia; HP:0000925 Abnormality of the vertebral column; HP:0002808 Kyphosis). (carvalho2020spondyloepimetaphysealdysplasiawith pages 1-3, kondo2018site1proteasedeficiency pages 1-2, raggio2024exomesequencingreveals pages 4-6) - Low bone mineral density / osteopenia (HP:0004349 Low bone mineral density; HP:0000938 Osteopenia). (carvalho2020spondyloepimetaphysealdysplasiawith pages 1-3, chen2023casereportrecombinant pages 4-6, raggio2024exomesequencingreveals pages 1-2) - Hernias (HP:0000023 Inguinal hernia; HP:0001537 Umbilical hernia). (chen2023casereportrecombinant pages 4-6, liaqat2024acaseof pages 1-2, raggio2024exomesequencingreveals pages 2-4) - Craniosynostosis (HP:0001363 Craniosynostosis) and epilepsy/seizures (HP:0001250 Seizures) in some cases. (carvalho2020spondyloepimetaphysealdysplasiawith pages 1-3) - Elevated plasma lysosomal enzymes with normal leukocyte enzyme activity (laboratory phenotype; map to LOINC/SNOMED locally). (carvalho2020spondyloepimetaphysealdysplasiawith pages 1-3, carvalho2020spondyloepimetaphysealdysplasiawith pages 3-4, kondo2018site1proteasedeficiency pages 1-2)

Recent quantitative statistics (2024): A 2024 case report summarizing previous cases reported that “80% had low stature, 70% low weight, 80% had bilateral cataracts and 70% showed Spondyloepiphyseal dysplasia on X-rays.” (Diagnostics; Jan 2024; https://doi.org/10.3390/diagnostics14030313) (raggio2024exomesequencingreveals pages 1-2)

Example laboratory values (2020 case report): multiple plasma lysosomal enzymes were markedly elevated; e.g., total plasma beta-hexosaminidases 3,975 nmol/h/ml (reference 400–1,400); iduronate-2-sulfatase 1,080 nmol/4 h/ml (reference 167–475); alpha-N-acetylgalactosaminidase 648 nmol/17 h/ml (reference 60–240). (carvalho2020spondyloepimetaphysealdysplasiawith pages 3-4)

4. Genetic / Molecular Information

4.1 Causal genes

4.2 Pathogenic variants and variant classes

AIFM1 entity (X-linked)

  • p.Asp237Gly in AIFM1 identified by WES as the single plausible candidate segregating with disease in two families; reported as novel and predicted pathogenic in silico. (mierzewska2017spondyloepimetaphysealdysplasiawith pages 1-2)
  • Multiple families show variants clustered at/near AIFM1 intron 6/exon 7 boundary, with evidence supporting exon 7 skipping as a shared pathogenic mechanism. (edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 1-4, edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 8-11)

MBTPS1 entity (autosomal recessive)

Primary literature variants include: - Homozygous nonsense: p.Trp983Ter (NM_003791.2 c.2948G>A; exon 22) (2020 case report). (carvalho2020spondyloepimetaphysealdysplasiawith pages 3-4) - Compound heterozygous (2024): c.2355delG p.Met785fs (frameshift, predicted NMD) and c.1094A>G p.Asp365Gly (missense). (raggio2024exomesequencingreveals pages 4-6) - Splice-altering synonymous: c.774C>T (p.A258=) causing exon 6 skipping (validated by transcript analysis/minigene assay; 2023). Abstract quote: “The transcript analysis in vivo exhibited that the synonymous variant c.774C > T caused exon 6 skipping. The minigene splice assay in vitro confirmed the alteration of MBTPS1 mRNA splicing…”. (Frontiers in Pediatrics; Jan 2023; https://doi.org/10.3389/fped.2022.1056141) (raggio2024exomesequencingreveals pages 1-2) - Compound heterozygous (2024): c.2255G>T p.(Gly752Val) and c.2831+5G>T with RNA-seq showing exon 21 skipping and predicted frameshift p.(Ser901fs28*) with nonsense-mediated decay. (liaqat2024acaseof pages 1-2) - First described S1P deficiency (2018): biallelic variants resulting in ~1% functional MBTPS1 transcripts. (kondo2018site1proteasedeficiency pages 1-2)

Population allele frequencies / ClinVar classifications were not directly retrievable from the current evidence set; therefore, ACMG category assertions are not made here.

4.3 Modifier genes / epigenetics / chromosomal abnormalities

No validated modifier genes, epigenetic signatures, or recurrent chromosomal abnormalities specific to SEMD-BT were identified in the retrieved primary literature in this run. (mierzewska2017spondyloepimetaphysealdysplasiawith pages 1-2, kondo2018site1proteasedeficiency pages 1-2)

5. Environmental Information

No non-genetic environmental contributors are established for these monogenic skeletal dysplasias in the retrieved evidence. (kondo2018site1proteasedeficiency pages 1-2)

6. Mechanism / Pathophysiology

6.1 MBTPS1 (Site-1 protease) deficiency: ER stress, collagen trafficking, and lysosomal enzyme mistargeting

Upstream trigger: biallelic MBTPS1 variants reduce functional S1P activity. (kondo2018site1proteasedeficiency pages 1-2)

Causal chain (proposed in primary literature): 1. Residual S1P activity may be sufficient for some systemic lipid homeostasis, but insufficient for ER and lysosomal functions in chondrocytes. (kondo2018site1proteasedeficiency pages 1-2) 2. Defective S1P impairs activation of the ER stress transducer BBF2H7, causing ER retention of collagen in chondrocytes. (kondo2018site1proteasedeficiency pages 1-2) 3. S1P deficiency partially impairs mannose-6-phosphate (M6P)-dependent delivery to lysosomes, resulting in abnormal secretion/elevation of lysosomal enzymes in blood. (kondo2018site1proteasedeficiency pages 1-2) 4. These combined defects contribute to chondrocyte apoptosis and lysosomal enzyme-mediated degradation of bone matrix, producing the skeletal dysplasia phenotype. (kondo2018site1proteasedeficiency pages 1-2)

Abstract quote (mechanistic): “The defective S1P function specifically impairs activation of the ER stress transducer BBF2H7, leading to ER retention of collagen in chondrocytes. S1P deficiency also causes abnormal secretion of lysosomal enzymes due to partial impairment of mannose-6-phosphate-dependent delivery to lysosomes.” (JCI Insight; Jul 2018; https://doi.org/10.1172/jci.insight.121596) (kondo2018site1proteasedeficiency pages 1-2)

Ontology suggestions: - GO Biological Process (examples): ER stress response; protein folding; collagen fibril organization; lysosomal transport; glycoprotein trafficking; chondrocyte apoptosis. - CL cell types (examples): chondrocyte (CL:0000138); osteoblast (CL:0000062). - UBERON (examples): cartilage (UBERON:0002416); growth plate cartilage (UBERON:0002597); vertebral column (UBERON:0001137).

6.2 AIFM1 exon 7-region variants: hypomyelination + skeletal dysplasia via tissue-specific AIFM1 effects

Primary literature supports a genotype–phenotype pattern in which variants near exon 7 (often splice-affecting) associate with the combined skeletal + hypomyelination syndrome, with evidence that exon 7 skipping is a common mechanism. (edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 1-4, edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 8-11)

Mechanistic interpretation (from authors): exon 7 of AIFM1 is proposed to be “integral to its functional role in cells involved in cartilage and bone development and turnover,” and RNA evidence supports aberrant splicing with exon 7 loss. (edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 8-11)

Ontology suggestions: - GO BP: myelination; mitochondrial respiratory chain complex assembly; apoptosis regulation. - CL: oligodendrocyte (CL:0000128); chondrocyte (CL:0000138). - UBERON: cerebral white matter (UBERON:0004706); cartilage; vertebral column.

7. Anatomical Structures Affected

7.1 Organ/system level

7.2 Tissue/cell level

7.3 Subcellular level (MBTPS1 mechanism)

8. Temporal Development

9. Inheritance and Population

9.1 Inheritance

9.2 Epidemiology

Formal prevalence/incidence estimates were not identified in the retrieved evidence; available data are case-based. - A 2021 review-style case expansion states “To date 19 patients from 8 families have been reported” for SMD-H (AIFM1 exon 7–region). (American Journal of Medical Genetics Part A; Jan 2021; https://doi.org/10.1002/ajmg.a.62072) (edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 1-4) - A 2024 MBTPS1 case report states it is (to their knowledge) the 7th molecularly confirmed SEDKF case worldwide (2018–2023) and the 10th case with MBTPS1-related phenotypes. (Diagnostics; Jan 2024; https://doi.org/10.3390/diagnostics14030313) (raggio2024exomesequencingreveals pages 4-6)

10. Diagnostics

10.1 Clinical and imaging diagnosis

10.2 Laboratory biomarkers

10.3 Genetic testing approach

10.4 Differential diagnosis

Differential considerations include other SEMD/SMD subtypes and lysosomal-storage-disorder-like phenocopies; an older SEMD radiologic review emphasizes distinguishing SEMD forms from Dyggve–Melchior–Clausen (DMC) by features such as the iliac crest “lacy” appearance, which was absent in the Bieganski-described neurocognitive SEMD form. (temtamy2007geneticheterogeneityin pages 18-20)

11. Outcomes / Prognosis

12. Treatment / Management

12.1 Disease-modifying / targeted therapy

No approved disease-modifying therapy was identified for either entity in the retrieved evidence.

12.2 Supportive and symptomatic management (real-world implementations)

12.3 Growth hormone (GH) therapy (reported application)

A 2023 case report describes recombinant human growth hormone (rhGH) treatment in MBTPS1-associated SEDKF, with the authors concluding: “Growth hormone therapy can repair growth retardation in patients with spondyloepiphyseal dysplasia, Kondo-Fu type; however, more evidence of such patient cases is required to support this hypothesis.” (Frontiers in Pediatrics; Feb 2023; https://doi.org/10.3389/fped.2023.1068718) (chen2023casereportrecombinant pages 4-6)

12.4 MAXO term suggestions (examples)

  • Cataract extraction (MAXO term for cataract surgery)
  • Treatment with recombinant human growth hormone (MAXO term for GH therapy)
  • Physical therapy / orthopedic surveillance
  • Antiseizure medication therapy

12.5 Clinical trials

A clinical trials registry search in this run did not yield clearly relevant interventional trials specifically for SEMD-BT/MBTPS1/AIFM1 skeletal dysplasia. (OpenTargets Search: spondyloepimetaphyseal dysplasia Bieganski type,spondyloepimetaphyseal dysplasia-MBTPS1)

13. Prevention

Primary prevention is not applicable for established Mendelian disorders, but genetic counseling and reproductive options (carrier testing in X-linked families; carrier testing and prenatal/preimplantation diagnosis in autosomal recessive MBTPS1 families) are the standard prevention framework; specific guidelines were not retrieved in the current evidence set. (temtamy2007geneticheterogeneityin pages 18-20, raggio2024exomesequencingreveals pages 4-6)

14. Other Species / Natural Disease

No naturally occurring veterinary analogs were identified in the retrieved evidence corpus.

15. Model Organisms

The retrieved primary mechanism paper emphasizes chondrocyte-specific vulnerability and includes experimental correction of variants and ER stress reduction to mitigate collagen-trafficking defects, implying utility of cellular models (patient-derived cells/chondrocytes) for mechanism and therapeutic screening. (kondo2018site1proteasedeficiency pages 1-2)

16. Recent developments and latest research (prioritize 2023–2024)

2023: Synonymous MBTPS1 variant proven pathogenic via splicing assays

A 2023 report provides direct functional evidence that a synonymous MBTPS1 variant (c.774C>T) is pathogenic by causing exon 6 skipping, validated in vivo and with a minigene assay, and notes partial restoration of exon inclusion with an antisense oligonucleotide in vitro. (Frontiers in Pediatrics; Jan 2023; https://doi.org/10.3389/fped.2022.1056141) (raggio2024exomesequencingreveals pages 1-2)

2024: Expanded MBTPS1 phenotype and variant spectrum

Expert perspective / authoritative synthesis

A key expert mechanistic statement from the 2018 JCI Insight paper is that these findings “define a new congenital human skeletal disorder” and “reveal that S1P is particularly required for skeletal development in humans.” (JCI Insight; Jul 2018; https://doi.org/10.1172/jci.insight.121596) (kondo2018site1proteasedeficiency pages 1-2)

Limitations of this report

  • Several requested identifiers (Orphanet, ICD-10/ICD-11, MeSH) and population allele frequency statistics (gnomAD) could not be confirmed from the retrievable evidence in this tool run; they are therefore not asserted.
  • Because the name “Bieganski type” is ambiguous across sources, a definitive single-entity KB entry should be anchored to one gene/OMIM/MONDO axis after curation; this report provides the evidence needed to make that disambiguation. (OpenTargets Search: spondyloepimetaphyseal dysplasia Bieganski type,spondyloepimetaphyseal dysplasia-MBTPS1, edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 1-4, raggio2024exomesequencingreveals pages 1-2, kondo2018site1proteasedeficiency pages 1-2)

References

  1. (mierzewska2017spondyloepimetaphysealdysplasiawith pages 1-2): H. Mierzewska, M. Rydzanicz, T. Biegański, J. Kosinska, M. Mierzewska‐Schmidt, A. Ługowska, A. Pollak, P. Stawiński, A. Walczak, A. Kędra, E. Obersztyn, E. Szczepanik, and R. Płoski. Spondyloepimetaphyseal dysplasia with neurodegeneration associated with aifm1 mutation – a novel phenotype of the mitochondrial disease. Clinical Genetics, 91:30-37, Jan 2017. URL: https://doi.org/10.1111/cge.12792, doi:10.1111/cge.12792. This article has 62 citations and is from a peer-reviewed journal.

  2. (edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 1-4): Katharine Edgerley, Angela Barnicoat, Amaka C. Offiah, Alistair D. Calder, Kshitij Mankad, Nicholas Simon Thomas, David J. Bunyan, Maggie Williams, Chris Buxton, Arniban Majumdar, Kayal Vijayakumar, Tom Hilliard, James Turner, Christine P. Burren, Fergal Monsell, and Sarah F. Smithson. Aifm1‐associated x‐linked spondylometaphyseal dysplasia with cerebral hypomyelination. American Journal of Medical Genetics Part A, 185:1228-1235, Jan 2021. URL: https://doi.org/10.1002/ajmg.a.62072, doi:10.1002/ajmg.a.62072. This article has 7 citations.

  3. (edgerley2021aifm1‐associatedx‐linkedspondylometaphyseal pages 8-11): Katharine Edgerley, Angela Barnicoat, Amaka C. Offiah, Alistair D. Calder, Kshitij Mankad, Nicholas Simon Thomas, David J. Bunyan, Maggie Williams, Chris Buxton, Arniban Majumdar, Kayal Vijayakumar, Tom Hilliard, James Turner, Christine P. Burren, Fergal Monsell, and Sarah F. Smithson. Aifm1‐associated x‐linked spondylometaphyseal dysplasia with cerebral hypomyelination. American Journal of Medical Genetics Part A, 185:1228-1235, Jan 2021. URL: https://doi.org/10.1002/ajmg.a.62072, doi:10.1002/ajmg.a.62072. This article has 7 citations.

  4. (raggio2024exomesequencingreveals pages 1-2): Víctor Raggio, Soledad Rodríguez, Sandra Feder, Rosario Gueçaimburú, and Lucía Spangenberg. Exome sequencing reveals biallelic mutations in mbtps1 gene in a girl with a very rare skeletal dysplasia. Diagnostics, 14:313, Jan 2024. URL: https://doi.org/10.3390/diagnostics14030313, doi:10.3390/diagnostics14030313. This article has 3 citations.

  5. (carvalho2020spondyloepimetaphysealdysplasiawith pages 1-3): Daniel R. Carvalho, Carlos E. Speck‐Martins, Jaime M. Brum, Carlos R. Ferreira, and Nara L. M. Sobreira. Spondyloepimetaphyseal dysplasia with elevated plasma lysosomal enzymes caused by homozygous variant in mbtps1. American Journal of Medical Genetics Part A, 182:1796-1800, May 2020. URL: https://doi.org/10.1002/ajmg.a.61614, doi:10.1002/ajmg.a.61614. This article has 23 citations.

  6. (kondo2018site1proteasedeficiency pages 1-2): Yuji Kondo, Jianxin Fu, Hua Wang, Christopher Hoover, J. Michael McDaniel, Richard Steet, Debabrata Patra, Jianhua Song, Laura Pollard, Sara Cathey, Tadayuki Yago, Graham Wiley, Susan Macwana, Joel Guthridge, Samuel McGee, Shibo Li, Courtney Griffin, Koichi Furukawa, Judith A. James, Changgeng Ruan, Rodger P. McEver, Klaas J. Wierenga, Patrick M. Gaffney, and Lijun Xia. Site-1 protease deficiency causes human skeletal dysplasia due to defective inter-organelle protein trafficking. JCI insight, Jul 2018. URL: https://doi.org/10.1172/jci.insight.121596, doi:10.1172/jci.insight.121596. This article has 68 citations and is from a domain leading peer-reviewed journal.

  7. (OpenTargets Search: spondyloepimetaphyseal dysplasia Bieganski type,spondyloepimetaphyseal dysplasia-MBTPS1): Open Targets Query (spondyloepimetaphyseal dysplasia Bieganski type,spondyloepimetaphyseal dysplasia-MBTPS1, 1 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

  8. (temtamy2007geneticheterogeneityin pages 18-20): SA Temtamy, MS Aglan, and MA El-Gammal. Genetic heterogeneity in spondylo-epimetaphyseal dysplasias: a clinical and radiological study. Unknown journal, 2007.

  9. (carvalho2020spondyloepimetaphysealdysplasiawith pages 3-4): Daniel R. Carvalho, Carlos E. Speck‐Martins, Jaime M. Brum, Carlos R. Ferreira, and Nara L. M. Sobreira. Spondyloepimetaphyseal dysplasia with elevated plasma lysosomal enzymes caused by homozygous variant in mbtps1. American Journal of Medical Genetics Part A, 182:1796-1800, May 2020. URL: https://doi.org/10.1002/ajmg.a.61614, doi:10.1002/ajmg.a.61614. This article has 23 citations.

  10. (chen2023casereportrecombinant pages 4-6): Congli Chen, Jin Wu, and Ying Liu. Case report: recombinant human growth hormone therapy in a patient with spondyloepiphyseal dysplasia, kondo-fu type. Frontiers in Pediatrics, Feb 2023. URL: https://doi.org/10.3389/fped.2023.1068718, doi:10.3389/fped.2023.1068718. This article has 8 citations.

  11. (raggio2024exomesequencingreveals pages 2-4): Víctor Raggio, Soledad Rodríguez, Sandra Feder, Rosario Gueçaimburú, and Lucía Spangenberg. Exome sequencing reveals biallelic mutations in mbtps1 gene in a girl with a very rare skeletal dysplasia. Diagnostics, 14:313, Jan 2024. URL: https://doi.org/10.3390/diagnostics14030313, doi:10.3390/diagnostics14030313. This article has 3 citations.

  12. (raggio2024exomesequencingreveals pages 4-6): Víctor Raggio, Soledad Rodríguez, Sandra Feder, Rosario Gueçaimburú, and Lucía Spangenberg. Exome sequencing reveals biallelic mutations in mbtps1 gene in a girl with a very rare skeletal dysplasia. Diagnostics, 14:313, Jan 2024. URL: https://doi.org/10.3390/diagnostics14030313, doi:10.3390/diagnostics14030313. This article has 3 citations.

  13. (liaqat2024acaseof pages 1-2): Khurram Liaqat, Kayla Treat, Lili Mantcheva, Abdul Nasir, David D. Weaver, Erin Conboy, and Francesco Vetrini. A case of mbtps1‐related disorder due to compound heterozygous variants in mbtps1 gene: genotype–phenotype expansion and the emergence of a novel syndrome. American Journal of Medical Genetics Part A, Dec 2024. URL: https://doi.org/10.1002/ajmg.a.63499, doi:10.1002/ajmg.a.63499. This article has 4 citations.