Liebenberg syndrome: brachydactyly with joint dysplasia (MIM 186550): a second family

Tiberio, G.; Digilio, M. Cristina; Graziani, M; Testa, F.; Giannotti, Aldo

doi:10.1136/jmg.37.7.548

Cited by 9 publications

(4 citation statements)

References 7 publications

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“…Male-to-male transmission suggested an autosomal dominant inheritance. Tiberio et al (2000) described a second family with an affected mother and two sons with clinical and radiological features closely resembling those described by Liebenberg. Subsequently, four more families were reported and the upper limb malformation came to be known as 'Liebenberg syndrome' (AbdelGhani et al, 2013;Di Gennaro et al, 2006;Spielmann et al, 2012).…”

Section: Introductionmentioning

confidence: 66%

The Liebenberg syndrome: in depth analysis of the original family

Mennen

Mundlos

Spielmann

2013

J Hand Surg Eur Vol

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The Liebenberg syndrome was first described in 1973 in a five- generation family. A sixth generation was added in 2001, and in 2009 a hitherto unknown branch of the same family with similar anomalies extended the family tree significantly. This article describes the clinical findings and illustrates the abnormalities with radiographs and three-dimensional computed tomography scans. We discuss the genetic abnormality that causes Liebenberg syndrome, the genomic rearrangement at the PITX1 locus on chromosome 5.The structural variations seem to result in an ectopic expression of paired-like homeodomain transcription factor 1 (PITX1) in the forelimb causing a partial arm-to-leg transformation in these patients.

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Section: Introductionmentioning

confidence: 66%

The Liebenberg syndrome: in depth analysis of the original family

Mennen

Mundlos

Spielmann

2013

J Hand Surg Eur Vol

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“…13 All three individuals display typical though mild arm-to-leg transformation affecting the lower arms: brachydactyly, camptodactyly of the fifth finger, fusion of proximal scaphoid and lunate, enlarged triquetrum, enlarged and dysplastic distal humerus that articulates with a reduced olecranon and the proximal radius forming a knee-like joint (figure 1B). Array-CGH (20 kb resolution) of individual II:2 was negative.…”

Section: Resultsmentioning

confidence: 99%

H2AFY promoter deletion causes PITX1 endoactivation and Liebenberg syndrome

et al. 2019

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BackgroundStructural variants (SVs) affecting non-coding cis-regulatory elements are a common cause of congenital limb malformation. Yet, the functional interpretation of these non-coding variants remains challenging. The human Liebenberg syndrome is characterised by a partial transformation of the arms into legs and has been shown to be caused by SVs at the PITX1 locus leading to its misregulation in the forelimb by its native enhancer element Pen. This study aims to elucidate the genetic cause of an unsolved family with a mild form of Liebenberg syndrome and investigate the role of promoters in long-range gene regulation.MethodsHere, we identify SVs by whole genome sequencing (WGS) and use CRISPR-Cas9 genome editing in transgenic mice to assign pathogenicity to the SVs.ResultsIn this study, we used WGS in a family with three mildly affected individuals with Liebenberg syndrome and identified the smallest deletion described so far including the first non-coding exon of H2AFY. To functionally characterise the variant, we re-engineered the 8.5 kb deletion using CRISPR-Cas9 technology in the mouse and showed that the promoter of the housekeeping gene H2afy insulates the Pen enhancer from Pitx1 in forelimbs; its loss leads to misexpression of Pitx1 by the pan-limb activity of the Pen enhancer causing Liebenberg syndrome.ConclusionOur data indicate that housekeeping promoters may titrate promiscuous enhancer activity to ensure normal morphogenesis. The deletion of the H2AFY promoter as a cause of Liebenberg syndrome highlights this new mutational mechanism and its role in congenital disease.

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“…The vertebrate embryology laboratory begins in a hospital room where a patient with Liebenberg Syndrome is being examined by the student and a medical doctor. Liebenberg Syndrome is a unique condition where the arms of a person resemble their legs [4]. The transmission of the disease is autosomal dominant and mutations that can cause this disease has recently been identified [5][6][7].…”

Section: Construction Of the Vertebrate Embryology Laboratory Using Tmentioning

confidence: 99%

“…To determine genes that, upon mutation, were potentially involved in arms resembling legs in humans (a characteristic of Liebenberg Syndrome [4]), mouse fore-and hindlimbs were dissected from embryos. The hypothesis being tested was that a gene(s) required for the development of these structures may be enriched in the forelimb or hindlimb.…”

Section: Construction Of the Vertebrate Embryology Laboratory Using Tmentioning

confidence: 99%

Design, construction, and advantages of 100% online laboratories in an upper division undergraduate biology course

Brady

Reeves

Maden

et al. 2020

Preprint

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For centuries, students have been taught by passively listening to lectures, usually in large groups. In many fields, this type of course delivery is not ideal. In addition, students that have grown up with online access and/or have been forced to take online course during the recent pandemic, are seeking improved online educational experiences. As providers of education, Universities must adapt to this rapidly changing environment. The emergence of exciting, “disruptive” technologies has provided the tools needed for educators to revolutionize the delivery of higher education. The University of Florida, through UF Online, provides students the opportunity to enroll in fully online four-year undergraduate degrees. In this report, we describe the development of fully online laboratories for the upper-division course Evolutionary Developmental Biology, which fulfill the University of Florida’s laboratory requirement. This course is taken by Biology, Zoology, and related majors, including majors in the 100% online Biology degree. The experiments in the virtual laboratories would have been impossible to teach in a residential setting due to time constraints, cost, student safety issues, and regulatory/certification requirements. The ability to perform these experiments online provided University of Florida undergraduates located throughout the world access to unique, one-of-a-kind laboratory experiences. The virtual laboratories allowed students to undertake in-depth exploration and application of course content that is not possible in a residential setting. Completion of the Evolutionary Developmental Biology course provided undergraduate students the opportunity to obtain a science degree without ever visiting the university’s residential campus. During the Fall 2020 term, this course was made available to residential students, thus allowing this cohort of students to continue to make progress, 100% online, towards their undergraduate degree during the COVID19 pandemic.

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Liebenberg syndrome: brachydactyly with joint dysplasia (MIM 186550): a second family

Cited by 9 publications

References 7 publications

The Liebenberg syndrome: in depth analysis of the original family

The Liebenberg syndrome: in depth analysis of the original family

H2AFY promoter deletion causes PITX1 endoactivation and Liebenberg syndrome

Design, construction, and advantages of 100% online laboratories in an upper division undergraduate biology course

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