PAPSS2 mutations cause autosomal recessive brachyolmia | Semantic Scholar (2024)

The findings indicate that autosomal dominant brachyolmia may be associated with significant long‐term morbidity, as seen in this family, and a wide range of subjective symptoms with chronic pain in the extremities and the spine, and paresthesias.

An autosomal recessive form of brachyolmia that is caused by loss‐of‐function mutations of PAPSS2, the gene encoding PAPS (3‐phosphoadenosine 5-phosphosulfate) synthase 2, is identified and is associated with abnormal androgen metabolism.

A missense mutation was identified in the PAPSS2 gene that caused Brachyolmia in a consanguineous Pakistani family and it was confirmed by the Sanger sequencing in the enrolled subjects.

An affected boy with AR-BO is reported, whose skeletal abnormalities were detected in utero and who was followed until 10years of age, and whose overall findings were consistent with known features of AR- BO.

An exome sequencing in two unrelated Japanese families with opsismodysplasia and identified a novel INPPL1 mutation, c.1960_1962delGAG, in one family further support that inositol polyphosphate phosphatase-like 1 is the disease gene for opsismo-somatica and that opsismic heterogeneity has genetic heterogeneity.

The study indicates that autosomal recessive brachyolmia occurs across continents and may be under‐recognized in infancy, and should be considered in the differential diagnosis of short femora presenting in the second trimester.

In conclusion, mutations of COL2A1, PHEX and COMP gene are common for short stature due to bone dysplasia in outpatient clinics in pediatric endocrinology.

This review discusses disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature.

RNA-sequencing-based transcriptome profiling of primary skin fibroblasts was performed to identify genes involved in cartilage physiology that are differentially expressed in MBTPS2-OI but not in MBTP/KFSD fibro Blasts, and observed that SREBP-dependent genes are more downregulated in OI than in IFAP/KfSD.

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A previously unknown mechanism, activation of a calcium-permeable TRP ion channel, in skeletal dysplasia pathogenesis is defined.

The hypothesis that a further condition, Spondylo‐epiphyseal dysplasia (SED), Maroteaux type (MIM 184095; also known as pseudo‐Morquio syndrome type 2), could be caused by TRPV4 mutations is tested and it is concluded that SED Maroteau type and parastremmatic dysplasticity are part of the TRPv4 Dysplasia family.

The cartilage-specificity of the human and mouse phenotypes provides further evidence of the critical role of sulfate activation in the maturation of cartilage extracellular matrix molecules and the effect of defects in this process on the architecture ofcartilage and skeletogenesis.

A large inbred kindred from a remote area of Pakistan, comprising eight generations, with a distinct form of spondyloepimetaphyseal dysplasia (SEMD), which strongly suggests autosomal recessive inheritance, and consanguineous loops could account for all the affected individuals being hom*ozygous for the abnormal allele.

Clinical, radiological, and genetic differences suggest genetic heterogeneity in this group of platyspondylic disorders.

Fetal akinesia as leading sign is unusual and suggests that certain TRPV4 mutations produce both chondrodysplasia and a peripheral neuropathy resulting in a severe “overlap” phenotype.

The entity described is set apart not only from the X‐linked and autosomal‐dominant forms of SED tarda but also from the already delineated autosomal recessive types by significant clinical and radiographic differences.

The radiological findings are compatible with brachyolmia, Hobaek type, which is characterized by platyspondyly, horizontal acetabular roof, short femoral neck, and vertical “mixed lucent and dense” striation pattern in the metaphyses of large long bones.

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