BMPR-IB gene disruption causes severe limb deformities in pigs

In an attempt to generate g.A746G substitution in the BMPR-IB gene,we unexpectedly obtained BMPR-IB homozygous knockout piglets(BMPR-IB^(-/-))and heterogeneous knockout piglets with one copy of the A746G mutation(BMPR-IB-/746G)via CRISPR/Cas9 editing.Polymerase chain reaction(PCR)and sequencing revealed complex genomic rearrangements in the target region.All BMPR-IBdisrupted piglets showed an inability to stand and walk normally.Both BMPR-IB^(-/-)and BMPR-IB-/746G piglets exhibited severe skeletal dysplasia characterized by distorted and truncated forearms(ulna,radius)and disordered carpal,metacarpal,and phalangeal bones in the forelimbs.The piglets displayed more severe deformities in the hindlimbs by visual inspection,including fibular hemimelia,enlarged tarsal bone,and disordered toe joint bones.Limb deformities were more profound in BMPR-IB^(-/-)piglets than in the BMPR-IB-/746G piglets.Proteomic analysis identified 139 differentially expressed proteins(DEPs)in the hindlimb fibula of BMPR-IB-/746G piglets compared to the wild-type(WT)controls.Most DEPs are involved in skeletal or embryonic development and/or the TGF-βpathway and tumor progression.Gene Ontology(GO)and protein domain enrichment analysis suggested alterations in these processes.Of the top 50 DEPs,a large proportion,e.g.,C1QA,MYO1H,SRSF1,P3H1,GJA1,TCOF1,RBM10,SPP2,MMP13,and PHAX,were significantly associated with skeletal development.Our study provides novel findings on the role of BMPR-IB in mammalian limb development.

Clinical Use of Extracorporeal Shockwave Therapy(ESWT)for the Treatment of Carpus Valgus Deformities in Young Foals:A Retrospective Study of 64 Cases(2006-2009)

The purpose of this study was to report the use and assess the effects of extracorporeal shockwave therapy (ESWT) for the treatment of carpal joint valgus deformities (CJVDs) in young foals. Only foals with CJVDs greater than 5° were included in the study. Foals were assigned to 3 treatment groups based on their degree of CJVD measured during the initial evaluation: valgus deformity (VD) of 5° to 8.9° (Group 1), VD of 9° to 11.9° (Group 2) and VD greater than or equal to 12° (Group 3). ESWT was applied on the convex side of the angular deformity immediately following the initial radiographic evaluation. Foals were subsequently evaluated clinically and radiologically followed by treatment every 10 days until resolution of the VD, with resolution defined as a deviation less than 5 degrees. Each treatment group received specific exercise, hoof trimming and hoof/shoe extension recommendations. Sixty-four (64) foals were included in the study;ages ranged from 8 to 60 days old at inclusion in the study with a mean age of 26.7 days. Of the 28 foals included in Group 1, 10 had bilateral CJVD. There were 21 in Group 2, and 15 in Group 3. Treatment success was defined as a VD angle less than 5°, and was reached in all foals in Groups 1 and 2. Five (5) foals in Group 3 completed the study with a VD angle of 5° to 6.7° at the last radiographic assessment. No major complications were observed during the study. In conclusion, ESWT in conjunction with controlled exercise, hoof trimming and hoof/shoe extensions corrected severe CJVDs in young foals. The use of ESWT eliminates possible negative side effects of general anesthesia and surgical techniques to treat VDs. Future studies should include a control population, more severe cases, other types of angular limb deformities, and older foals.

Prenatal diagnosis of triphalangeal thumb-polysyndactyly syndrome by ultrasonography combined with genetic testing:A case report

BACKGROUND Triphalangeal thumb-polysyndactyly syndrome(TPT-PS)is a rare type of congenital limb deformity,and most studies focus on the genetics.Case reports of the sonographic characteristics of TPT-PS during pregnancy are rare.CASE SUMMARY A 30-year-old woman(G3P1)who had pregnancies with TPT-PS fetuses is presented.The possibility of TPT-PS was shown by ultrasound performed at the 19th wk of pregnancy,featuring hands with six metacarpals,an extra digit at the 5th finger side,and an abnormally widened thumb.Whole-exome sequencing was subsequently conducted.The results showed that exons 1-17 of the LMBR1 gene had a heterozygous duplication,with a length of approximately 253 kb.CONCLUSION We suggest prenatal ultrasound examination combined with genetic testing to diagnose TPT-PS accurately and to help clinicians and patients make decisions.

Coronal plane deformity around the knee in the skeletally immature population:A review of principles of evaluation and treatment

Coronal plane deformity around the knee,also known as genu varum or genu valgum,is a common finding in clinical practice for pediatricians and orthopedists.These deformities can be physiological or pathological.If untreated,pathological deformities can lead to abnormal joint loading and a consequent risk of premature osteoarthritis.The aim of this review is to provide a framework for the diagnosis and management of genu varum and genu valgum in skeletally immature patients.