Skeletal Dysplasias: An Overview

Offiah, A.C.

doi:10.1159/000381051

Cited by 22 publications

(18 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, our findings suggest that BMP4 may be essential for maintaining normal human bone density. Similar to tooth agenesis, familiar osteoporosis also has a strong genetic predisposition (Offiah, 2015). Loss-of-function mutations of proteins in the Wnt pathway, WNT1 (Kampe, Makitie, & Makitie, 2015) and LRP5 (Biha, Ghaber, Hacen, & Collet, 2016), have been shown to cause juvenile osteoporosis, while a heterozygous duplication of BMP2 (Su et al, 2011) was found in a patient with brachydactyly, a congenital deformity of the digits.…”

Section: Discussionmentioning

confidence: 99%

BMP4 mutations in tooth agenesis and low bone mass

Wang

Fan

et al. 2019

Archives of Oral Biology

View full text Add to dashboard Cite

Objective: To identify an uncommon genetic cause of tooth agenesis (TA) by utilizing whole exome sequencing (WES) and targeted Sanger sequencing in a cohort of 120 patients with isolated TA. Design: One deleterious mutation in the gene encoding bone morphogenetic protein 4 (BMP4) was identified in 6 unrelated patients with TA by whole exome sequencing. After the detection of the BMP4 mutation, the coding exons of BMP4 was examined in 114 TA patients using Sanger sequencing. Dual-energy X-ray absorptiometry (DEXA) was used to measure the bone mineral density of patients who carried a BMP4 mutation. Finally, preliminary functional studies of two BMP4 mutants were performed. Results: We detected 3 novel missense mutations (c.58G>A: p.Gly20Ser, c.326G>T: p.Arg109Leu and c.614T>C: p.Val205Ala) and 1 reported mutation in the BMP4 gene among 120 TA probands. The previously reported BMP4 mutation (c.751C>T: p.His251Tyr) was associated with urethra and eye anomalies. By extending the pedigrees, we determined that the tooth phenotypes had an autosomal dominant inheritance pattern, as individuals carrying a BMP4 mutation exhibit different types of dental anomalies. Interestingly, we observed that patients harboring a BMP4 mutation manifested early onset osteopenia or osteoporosis. Further in vitro functional assays demonstrated that two BMP4 mutants resulted in a decreased activation of Smad signaling. Therefore, a loss-of-function in BMP4 may contribute to the clinical phenotypes seen in this study. Conclusions: We identified 4 mutations in the BMP4 gene in 120 TA patients. To our knowledge, this is the first study to describe human skeletal diseases associated with BMP4 mutations.

show abstract

Section: Discussionmentioning

confidence: 99%

BMP4 mutations in tooth agenesis and low bone mass

Wang

Fan

et al. 2019

Archives of Oral Biology

View full text Add to dashboard Cite

show abstract

“…However, only a small part of these disorders has clear molecular pathogenesis [5]. Moreover, skeletal involvement may also occur in other multisystem syndromes [6]. Therefore, due to the clinical and genetic heterogeneity of SDs, it is very challenging to make a clear diagnosis, particularly in the prenatal diagnosis of fetal SDs.…”

Section: Introductionmentioning

confidence: 99%

Genetic Analysis in Fetal Skeletal Dysplasias by Trio Whole-Exome Sequencing

Yang

Shen

Yan

et al. 2019

BioMed Research International

View full text Add to dashboard Cite

Skeletal dysplasias (SDs) comprise a series of severe congenital disorders that have strong clinical heterogeneity and usually attribute to diverse genetic variations. The pathogenesis of more than half of SDs remains unclear. Additionally, the clinical manifestations of fetal SDs are ambiguous, which poses a big challenge for accurate diagnosis. In this study, eight unrelated families with fetal SD were recruited and subjected to sequential tests including chromosomal karyotyping, chromosomal microarray analysis (CMA), and trio whole-exome sequencing (WES). Sanger sequencing and quantitative fluorescence PCR (QF-PCR) were performed as affirmative experiments. In six families, a total of six pathogenic/likely pathogenic variations were identified in four genes including SLC26A2, FGFR3, FLNB, and TMEM38B. These variations caused disorders following autosomal dominant or autosomal recessive inheritance patterns, respectively. The results provided reliable evidence for the subsequent genetic counseling and reproductive options to these families. With its advantage in variation calling and interpreting, trio WES is a promising strategy for the investigation of fetal SDs in cases with normal karyotyping and CMA results. It has considerable prospects to be utilized in prenatal diagnosis.

show abstract

“…These are most useful over 8 weeks gestation, given the lack of skeletal ossification prior to this age [51]. It is also important to remember that although isolated limb anomalies may be more commonly encountered in live cases [52], lethal skeletal dysplasias will be more prevalent in the subgroup presenting for post-mortem imaging [53] so an entire overview of the body is usually necessary rather than imaging of the affected limb(s). Whilst PMUS can be useful in demonstrating the non-ossified, cartilaginous anatomy which is not present on radiography (Fig.…”

Section: Systems Reviewmentioning

confidence: 99%

Perinatal post-mortem ultrasound (PMUS): radiological-pathological correlation

2019

View full text Add to dashboard Cite

There has been an increasing demand and interest in post-mortem imaging techniques, either as an adjunct or replacement for the conventional invasive autopsy. Post-mortem ultrasound (PMUS) is easily accessible and more affordable than other cross-sectional imaging modalities and allows visualisation of normal anatomical structures of the brain, thorax and abdomen in perinatal cases. The lack of aeration of post-mortem foetal lungs provides a good sonographic window for assessment of the heart and normal pulmonary lobulation, in contrast to live neonates. In a previous article within this journal, we published a practical approach to conducting a comprehensive PMUS examination. This covered the basic principles behind why post-mortem imaging is performed, helpful techniques for obtaining optimal PMUS images, and the expected normal post-mortem changes seen in perinatal deaths. In this article, we build upon this by focusing on commonly encountered pathologies on PMUS and compare these to autopsy and other post-mortem imaging modalities.

show abstract

Skeletal Dysplasias: An Overview

Cited by 22 publications

References 37 publications

BMP4 mutations in tooth agenesis and low bone mass

BMP4 mutations in tooth agenesis and low bone mass

Genetic Analysis in Fetal Skeletal Dysplasias by Trio Whole-Exome Sequencing

Perinatal post-mortem ultrasound (PMUS): radiological-pathological correlation

Contact Info

Product

Resources

About