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Novel compound heterozygous pathogenic variants in ASCC1 in a Chinese patient with spinal muscular atrophy with congenital bone fractures 2 : evidence supporting a "Definitive" gene-disease relationship
Yiping Shen
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5820-0839
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: A very limited spectrum of ASCC1 pathogenic variants had been reported in five (mostly consanguineous) families with spinal muscular atrophy with congenital bone fractures 2 [OMIM #616867] since 2016.
Methods:A proband from a non-consanguineous Chinese family presented with neonatal severe hypotonia, respiratory distress, muscle weakness and atrophy, as well as congenital bone fractures was examined by exome sequencing.
Results: A compound heterozygosity of a nonsense (c.932C>G ,p.Ser311Ter) and an exon 5 deletion in ASCC1 segregating with phenotypes was detected, both variants are novel and pathogenic. Since ASCC1 is a relative new disease gene, we performed the gene curation following ClinGen SOP. The existing evidence is sufficient to support a "Definitive" level of disease-gene relationship.
Conclusion: This case report expended the mutation spectrum of ASCC1 and support the notion that this novel disease also occur in outbreed populations and this is a rare disease but may still be underdiagnosed due to its perinatal lethal outcomes.
Keywords: spinal muscular atrophy with congenital bone fractures 2; ASCC1 ; compound heterozygous; gene curation; exome sequencing
Keywords
spinal muscular atrophy with congenital bone fractures 2, ASCC1 , compound heterozygous, gene curation, exome sequencing
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Research
Novel compound heterozygous pathogenic variants in ASCC1 in a Chinese patient with spinal muscular atrophy with congenital bone fractures 2 : evidence supporting a "Definitive" gene-disease relationship
Yiping Shen
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5820-0839
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 30 Dec, 2019
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: A very limited spectrum of ASCC1 pathogenic variants had been reported in five (mostly consanguineous) families with spinal muscular atrophy with congenital bone fractures 2 [OMIM #616867] since 2016.
Methods:A proband from a non-consanguineous Chinese family presented with neonatal severe hypotonia, respiratory distress, muscle weakness and atrophy, as well as congenital bone fractures was examined by exome sequencing.
Results: A compound heterozygosity of a nonsense (c.932C>G ,p.Ser311Ter) and an exon 5 deletion in ASCC1 segregating with phenotypes was detected, both variants are novel and pathogenic. Since ASCC1 is a relative new disease gene, we performed the gene curation following ClinGen SOP. The existing evidence is sufficient to support a "Definitive" level of disease-gene relationship.
Conclusion: This case report expended the mutation spectrum of ASCC1 and support the notion that this novel disease also occur in outbreed populations and this is a rare disease but may still be underdiagnosed due to its perinatal lethal outcomes.
Keywords: spinal muscular atrophy with congenital bone fractures 2; ASCC1 ; compound heterozygous; gene curation; exome sequencing
Figure 1
Figure 2
Figure 3