scholarly journals A De Novo Mutation in COL1A1 in a Holstein Calf with Osteogenesis Imperfecta Type II

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 561
Author(s):  
Joana G. P. Jacinto ◽  
Irene M. Häfliger ◽  
Fintan J. McEvoy ◽  
Cord Drögemüller ◽  
Jørgen S. Agerholm
Keyword(s):  
Osteogenesis Imperfecta ◽  
De Novo ◽  
Perinatal Death ◽  
Genetic Disorders ◽  
Missense Variant ◽  
Connective Tissue Disorder ◽  
De Novo Mutation ◽  
Osteogenesis Imperfecta Type ◽  
Fibrillar Collagen ◽  
Type Ii

Osteogenesis imperfecta (OI) type II is a genetic connective tissue disorder characterized by bone fragility, severe skeletal deformities and shortened limbs. OI usually causes perinatal death of affected individuals. OI type II diagnosis in humans is established by the identification of heterozygous mutations in genes coding for collagens. The purpose of this study was to characterize the pathological phenotype of an OI type II-affected neonatal Holstein calf and to identify the causative genetic variant by whole-genome sequencing (WGS). The calf had acute as well as intrauterine fractures, abnormally shaped long bones and localized arthrogryposis. Genetic analysis revealed a private heterozygous missense variant in COL1A1 (c.3917T>A) located in the fibrillar collagen NC1 domain (p.Val1306Glu) that most likely occurred de novo. This confirmed the diagnosis of OI type II and represents the first report of a pathogenic variant in the fibrillar collagen NC domain of COL1A1 associated to OI type II in domestic animals. Furthermore, this study highlights the utility of WGS-based precise diagnostics for understanding congenital disorders in cattle and the need for continued surveillance for rare lethal genetic disorders in cattle.

scholarly journals A large deletion in the COL2A1 gene expands the spectrum of pathogenic variants causing bulldog calf syndrome in cattle

2020 ◽  
Vol 62 (1) ◽  
Author(s):  
Joana Gonçalves Pontes Jacinto ◽  
Irene Monika Häfliger ◽  
Anna Letko ◽  
Cord Drögemüller ◽  
Jørgen Steen Agerholm
Keyword(s):  
De Novo ◽  
Genetic Disorders ◽  
Polymerase Chain Reaction Analysis ◽  
Large Deletion ◽  
Whole Genome Sequence ◽  
De Novo Mutation ◽  
Loss Of Function ◽  
Single Nucleotide Variants ◽  
Pathogenic Variants ◽  
Base Pair Deletion

Abstract Background Congenital bovine chondrodysplasia, also known as bulldog calf syndrome, is characterized by disproportionate growth of bones resulting in a shortened and compressed body, mainly due to reduced length of the spine and the long bones of the limbs. In addition, severe facial dysmorphisms including palatoschisis and shortening of the viscerocranium are present. Abnormalities in the gene collagen type II alpha 1 chain (COL2A1) have been associated with some cases of the bulldog calf syndrome. Until now, six pathogenic single-nucleotide variants have been found in COL2A1. Here we present a novel variant in COL2A1 of a Holstein calf and provide an overview of the phenotypic and allelic heterogeneity of the COL2A1-related bulldog calf syndrome in cattle. Case presentation The calf was aborted at gestation day 264 and showed generalized disproportionate dwarfism, with a shortened compressed body and limbs, and dysplasia of the viscerocranium; a phenotype resembling bulldog calf syndrome due to an abnormality in COL2A1. Whole-genome sequence (WGS) data was obtained and revealed a heterozygous 3513 base pair deletion encompassing 10 of the 54 coding exons of COL2A1. Polymerase chain reaction analysis and Sanger sequencing confirmed the breakpoints of the deletion and its absence in the genomes of both parents. Conclusions The pathological and genetic findings were consistent with a case of “bulldog calf syndrome”. The identified variant causing the syndrome was the result of a de novo mutation event that either occurred post-zygotically in the developing embryo or was inherited because of low-level mosaicism in one of the parents. The identified loss-of-function variant is pathogenic due to COL2A1 haploinsufficiency and represents the first structural variant causing bulldog calf syndrome in cattle. Furthermore, this case report highlights the utility of WGS-based precise diagnostics for understanding congenital disorders in cattle and the need for continued surveillance for genetic disorders in cattle.

Osteogenesis imperfecta type II delineation of the phenotype with reference to genetic heterogeneity

1984 ◽  
Vol 17 (2) ◽  
pp. 407-423 ◽  
Author(s):  
D. O. Sillence ◽  
K. K. Barlow ◽  
A. P. Garber ◽  
J. G. Hall ◽  
D. L. Rimoin
Keyword(s):  
Osteogenesis Imperfecta ◽  
Genetic Heterogeneity ◽  
Osteogenesis Imperfecta Type ◽  
Type Ii

Osteogenesis imperfecta type II: prenatal sonographic diagnosis.

Radiology ◽  
1990 ◽  
Vol 174 (1) ◽  
pp. 181-185 ◽  
Author(s):  
C Munoz ◽  
R A Filly ◽  
M S Golbus
Keyword(s):  
Osteogenesis Imperfecta ◽  
Osteogenesis Imperfecta Type ◽  
Type Ii ◽  
Sonographic Diagnosis

Aortic Elastin Abnormalities in Osteogenesis Imperfecta Type II

1986 ◽  
Vol 6 (5) ◽  
pp. 409-421 ◽  
Author(s):  
I. Pasquali-Ronchetti ◽  
D. Quaglino ◽  
M. Baccarani-Contra ◽  
R. Tenconi ◽  
G.M. Bressan ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Osteogenesis Imperfecta Type ◽  
Type Ii

A Case of Osteogenesis Imperfecta Type II Caused by a Novel COL1A2 Gene Mutation: Endoscopic Third Ventriculostomy to Prevent Hydrocephalus

2012 ◽  
Vol 43 (04) ◽  
pp. 225-228
Author(s):  
Yasuo Hachiya ◽  
Masaharu Hayashi ◽  
Takashi Negishi ◽  
Soh Atsumi ◽  
Masaya Kubota ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Gene Mutation ◽  
Endoscopic Third Ventriculostomy ◽  
Third Ventriculostomy ◽  
Osteogenesis Imperfecta Type ◽  
Type Ii ◽  
Col1a2 Gene
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