Brachyolmia Type 2

Last update 01 Nov 2024

Basic Info

Synonyms

BCYM2, BRACHYOLMIA TYPE 2, BRACHYOLMIA, MAROTEAUX TYPE

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Introduction

A rare genetic spondylodysplastic dysplasia characterized by short trunk/short stature, generalized platyspondyly with rounding of vertebral bodies. The vertebral bodies show less elongation compared to patients with other types of the disorder. Precocious calcification of the cerebral falx and non-specific minor facial anomalies may be associated. There have been no new reports since 1989.

100 Clinical Results associated with Brachyolmia Type 2

100 Translational Medicine associated with Brachyolmia Type 2

0 Patents (Medical) associated with Brachyolmia Type 2

Literatures (Medical) associated with Brachyolmia Type 2

01 Jun 2010·American Journal of Medical Genetics Part AQ3 · BIOLOGY

Spondylo‐epiphyseal dysplasia, Maroteaux type (pseudo‐Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations

Q3 · BIOLOGY

Article

Author: Tae Joon Cho ; Jin Dai ; Sheila Unger ; Bernhard Zabel ; Francesco Benedicenti ; Ok Hwa Kim ; Maren Schmidt-Rimpler ; Francesca Bedeschi ; Roberto Mendoza-Londono ; Margherita Silengo ; Shiro Ikegawa ; Gen Nishimura ; André Megarbané ; Hiroshi Kitoh ; Ekkehart Lausch ; Jurgen Spranger ; Andrea Superti-Furga

AbstractRecent discoveries have established the existence of a family of skeletal dysplasias caused by dominant mutations in TRPV4. This family comprises, in order of increasing severity, dominant brachyolmia, spondylo‐metaphyseal dysplasia Kozlowski type, and metatropic dysplasia. We tested 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. We analyzed six individuals with Maroteaux type SED, including three who had previously been reported. All six patients were found to have heterozygous TRPV4 mutations; three patients had unreported mutations, while three patients had mutations previously described in association with metatropic dysplasia. In addition, we tested one individual with a distinct rare disorder, parastremmatic dysplasia (MIM 168400). This patient had a common, recurrent mutation seen in several patients with Kozlowski type spondylo‐metaphyseal dysplasia. We conclude that SED Maroteaux type and parastremmatic dysplasia are part of the TRPV4 dysplasia family and that TRPV4 mutations show considerable variability in phenotypic expression resulting in distinct clinical‐radiographic phenotypes. © 2010 Wiley‐Liss, Inc.

Frontiers in Cell and Developmental Biology

Unveiling the pathogenic mechanisms of NPR2 missense variants: insights into the genotype-associated severity in acromesomelic dysplasia and short stature

Article

Author: Al-Dirbashi, Ghayth ; Alshamsi, Alreem R ; Badawi, Sally ; Varghese, Divya Saro ; Ouda, Sara H ; Raj, Anjana ; Al-Ghamari, Ahmed J ; Ali, Bassam R ; John, Anne ; Al-Musafir, Hamda S

Introduction: Natriuretic peptide receptor 2 (NPR2 or NPR-B) plays a central role in growth development and bone morphogenesis and therefore loss-of-function variations in NPR2 gene have been reported to cause Acromesomelic Dysplasia, Maroteaux type 1 and short stature. While several hypotheses have been proposed to underlie the pathogenic mechanisms responsible for these conditions, the exact mechanisms, and functional characteristics of many of those variants and their correlations with the clinical manifestations have not been fully established.Methods: In this study, we examined eight NPR2 genetic missense variants (p.Leu51Pro, p.Gly123Val, p.Leu314Arg, p.Arg318Gly, p.Arg388Gln, p.Arg495Cys, p.Arg557His, and p.Arg932Cys) Acromesomelic Dysplasia, Maroteaux type 1 and short stature located on diverse domains and broadly classified as variants of uncertain significance. The evaluated variants are either reported in patients with acromesomelic dysplasia in the homozygous state or short stature in the heterozygous state. Our investigation included the evaluation of their expression, subcellular trafficking and localization, N-glycosylation profiles, and cyclic guanosine monophosphate (cGMP) production activity.Results and Discussion: Our results indicate that variants p.Leu51Pro, p.Gly123Val, p.Leu314Arg, p.Arg388Gln have defective cellular trafficking, being sequestered within the endoplasmic reticulum (ER), and consequently impaired cGMP production ability. Conversely, variants p.Arg318Gly, p.Arg495Cys, and p.Arg557His seem to display a non-statistically significant behavior that is slightly comparable to WT-NPR2. On the other hand, p.Arg932Cys which is located within the guanylyl cyclase active site displayed normal cellular trafficking profile albeit with defective cGMP. Collectively, our data highlights the genotype-phenotype relationship that might be responsible for the milder symptoms observed in short stature compared to acromesomelic dysplasia. This study enhances our understanding of the functional consequences of several NPR2 variants, shedding light on their mechanisms and roles in related genetic disorders which might also help in their pathogenicity re-classification.

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Brachyolmia Type 2

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