Dataset Information

A 20 bp Duplication in Exon 2 of the Aristaless-Like Homeobox 4 Gene (ALX4) Is the Candidate Causative Mutation for Tibial Hemimelia Syndrome in Galloway Cattle.

ABSTRACT: Aristaless-like homeobox 4 (ALX4) gene is an important transcription regulator in skull and limb development. In humans and mice ALX4 mutations or loss of function result in a number of skeletal and organ malformations, including polydactyly, tibial hemimelia, omphalocele, biparietal foramina, impaired mammary epithelial morphogenesis, alopecia, coronal craniosynostosis, hypertelorism, depressed nasal bridge and ridge, bifid nasal tip, hypogonadism, and body agenesis. Here we show that a complex skeletal malformation of the hind limb in Galloway cattle together with other developmental anomalies is a recessive autosomal disorder most likely caused by a duplication of 20 bp in exon 2 of the bovine ALX4 gene. A second duplication of 34 bp in exon 4 of the same gene has no known effect, although both duplications result in a frameshift and premature stop codon leading to a truncated protein. Genotyping of 1,688 Black/Red/Belted/Riggit Galloway (GA) and 289 White Galloway (WGA) cattle showed that the duplication in exon 2 has allele frequencies of 1% in GA and 6% in WGA and the duplication in exon 4 has frequencies of 23% in GA and 38% in WGA. Both duplications were not detected in 876 randomly selected German Holstein Friesian and 86 cattle of 21 other breeds. Hence, we have identified a candidate causative mutation for tibial hemimelia syndrome in Galloway cattle and selection against this mutation can be used to eliminate the mutant allele from the breed.

SUBMITTER: Brenig B

PROVIDER: S-EPMC4468193 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A 20 bp Duplication in Exon 2 of the Aristaless-Like Homeobox 4 Gene (ALX4) Is the Candidate Causative Mutation for Tibial Hemimelia Syndrome in Galloway Cattle.

Brenig Bertram B Schütz Ekkehard E Hardt Michael M Scheuermann Petra P Freick Markus M

PloS one 20150615 6

Aristaless-like homeobox 4 (ALX4) gene is an important transcription regulator in skull and limb development. In humans and mice ALX4 mutations or loss of function result in a number of skeletal and organ malformations, including polydactyly, tibial hemimelia, omphalocele, biparietal foramina, impaired mammary epithelial morphogenesis, alopecia, coronal craniosynostosis, hypertelorism, depressed nasal bridge and ridge, bifid nasal tip, hypogonadism, and body agenesis. Here we show that a complex ...[more]

PMID: 26076463

Similar Datasets

Project description:RationaleTibial hemimelia is known as a rare congenital lower limb deficiency. It has been classified into different types based on Jones classification, and the traditional treatment of tibial hemimelia is amputation. Here we present a variant and unclassified case of tibial hemimelia, which was caused by osteomyelitis. And the lower limb with tibial hemimelia was salvaged by asymmetric limb lengthening.Patient concerns19-year-old girl had the shortened and curved left lower extremity with walking abnormalities.DiagnosisThe patient's deformity was caused by osteomyelitis of tibia occurred when she was 18 month old. The tibial shaft was absent, while the proximal and distal tibia was present but was hypoplastic with radiographic analysis. The fibula was hypertrophied and curved like the capital letter C. The leg length discrepancy (LLD), mostly coming from the left lower leg, was 22 cm.InterventionsWe were able to salvage the limb successfully by 5 operations, including releasing soft tissue, fusing the proximal tibiofibular joint, fibular osteotomy, femur lengthening, and fibular lengthening.OutcomesThe whole treatment time for the patient was 3 years and 2 months, and she was followed up for 5 years afterward. The length of femur lengthening and fibula lengthening during the reconstruction were 7.8 cm and 11 cm, respectively. Most of the deformities were corrected, except that the left lower limb was still 2 cm shorter than the contralateral limb, and the 34 mm of mechanical axis deviation (MAD) of left lower limb remained. The reason why the patient's lower limbs were asymmetric was that the femur and fibular lengthening were performed within the affected limb only. Overall, the patient was very satisfied with her asymmetric limbs and its function after surgeries.LessonsThe LLD in this case mainly came from tibial hemimelia. However, the fibula was unable to be lengthened to 22 cm during the lower leg distraction process because of blood flow disturbance. We could only lengthen the femur to salvage the limb in this situation. Even though the patient still had a few residual deformities and a pair of asymmetric lower limbs, she was satisfied with the function and appearance of the reconstructed limb. Therefore, the lower limb with tibial hemimelia can be salvaged by asymmetric limb lengthening in special cases.

Project description:PurposeFibular hemimelia has denoted a spectrum of postaxial longitudinal deficiency with fibular aplasia/hypoplasia; the term "terminal hemimelia" is reserved for patients with postaxial longitudinal deficiency having a normal fibula. We aimed to delineate the characteristics of terminal hemimelia.MethodsIn total, 30 patients with postaxial longitudinal deficiency who had a normal or hypoplastic fibula and visited our institution between 1992 and 2022 were reviewed. Patients were divided into terminal hemimelia and classic fibular hemimelia groups, and their demographic characteristics and clinical and radiographic findings were compared.ResultsFemoral shortening, knee valgus, and tibial spine hypoplasia were less common in terminal hemimelia (n = 13) than in classic fibular hemimelia (n = 17) (p = 0.03, p < 0.001, and p = 0.003, respectively). None of the patients in the terminal hemimelia group exhibited knee instability, whereas 12% of patients with classic fibular hemimelia did. Ball-and-socket ankle and absence of lateral rays were commonly observed in both groups. However, tarsal coalition was observed less frequently in terminal hemimelia (p = 0.004). All terminal hemimelia patients exhibited a painless plantigrade foot without ankle instability. Despite limb-length discrepancy at maturity averaging 40.4 mm for terminal hemimelia and 67.0 mm for classic fibular hemimelia (p < 0.001), patients with terminal hemimelia, except for one, exhibited > 20 mm of limb-length discrepancy. However, 46% of them underwent limb-length equalization procedures, mostly single-stage tibial lengthening, at a mean age of 11.2 years.ConclusionTerminal hemimelia may present with a milder phenotype than classic fibular hemimelia. It mainly overlaps with the symptoms of fibular hemimelia below the ankle joint and manifests as limb-length discrepancy. However, a considerable number of patients with terminal hemimelia required limb-length equalization procedures, for example single-stage tibial lengthening.Level of evidencelevel IV.

Dataset Information

A 20 bp Duplication in Exon 2 of the Aristaless-Like Homeobox 4 Gene (ALX4) Is the Candidate Causative Mutation for Tibial Hemimelia Syndrome in Galloway Cattle.

Publications

A 20 bp Duplication in Exon 2 of the Aristaless-Like Homeobox 4 Gene (ALX4) Is the Candidate Causative Mutation for Tibial Hemimelia Syndrome in Galloway Cattle.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets