Novel spondyloepimetaphyseal dysplasia due to UFSP2 gene mutation

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Beukes hip dysplasia is an autosomal dominant disease which has to date been described only in a large South African family of Dutch origin. The patients presented with progressive epiphyseal dysplasia limited to femoral capital epiphysis and their height was not significantly reduced. A unique variant of the ubiquitin-fold modifier 1 (Ufm1)-specific peptidase 2 (UFSP2) gene (c.868T>C) has been reported in all individuals from Beukes family with clinical and radiological diagnosis of Beukes hip dysplasia. Three individuals, propositus, mother, and grandmother, presented with short stature, joint pain, genu vara and a novel spondyloepimetaphyseal dysplasia involving epiphyses predominantly at hips, but also at knees, ankles, wrists and hands, associated with variable degrees of metaphysis and spine involvement. Exome sequencing allowed us to identify the heterozygous variant c.1277A>C of the UFSP2 gene, leading to the missense change p.D426A, in all 3 patients. This mutation is predicted as damaging and, similarly to the mutation originally described in the Beukes family (p. Y290H), directly affects one of the catalytic residues participating in the active site of the protein. This supports the novel notion that loss of catalytic UFSP2 activity, observed in association with different mutants and already experimentally proven in vitro, may have different clinical outcomes.

Original languageEnglish
Pages (from-to)671-674
Number of pages4
JournalClinical Genetics
Volume93
Issue number3
DOIs
Publication statusPublished - Mar 1 2018

Fingerprint

Epiphyses
Hip Dislocation
Peptide Hydrolases
Mutation
Genes
Exome
Arthralgia
Ubiquitin
Thigh
Wrist
Ankle
Hip
Catalytic Domain
Knee
Spine
Hand
Economics
Mothers
Proteins
In Vitro Techniques

Keywords

  • skeletal dysplasia
  • spondyloepimetaphyseal dysplasia
  • UFSP2 gene

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

@article{6bfed4f868a545a8bef76b6586d5f240,
title = "Novel spondyloepimetaphyseal dysplasia due to UFSP2 gene mutation",
abstract = "Beukes hip dysplasia is an autosomal dominant disease which has to date been described only in a large South African family of Dutch origin. The patients presented with progressive epiphyseal dysplasia limited to femoral capital epiphysis and their height was not significantly reduced. A unique variant of the ubiquitin-fold modifier 1 (Ufm1)-specific peptidase 2 (UFSP2) gene (c.868T>C) has been reported in all individuals from Beukes family with clinical and radiological diagnosis of Beukes hip dysplasia. Three individuals, propositus, mother, and grandmother, presented with short stature, joint pain, genu vara and a novel spondyloepimetaphyseal dysplasia involving epiphyses predominantly at hips, but also at knees, ankles, wrists and hands, associated with variable degrees of metaphysis and spine involvement. Exome sequencing allowed us to identify the heterozygous variant c.1277A>C of the UFSP2 gene, leading to the missense change p.D426A, in all 3 patients. This mutation is predicted as damaging and, similarly to the mutation originally described in the Beukes family (p. Y290H), directly affects one of the catalytic residues participating in the active site of the protein. This supports the novel notion that loss of catalytic UFSP2 activity, observed in association with different mutants and already experimentally proven in vitro, may have different clinical outcomes.",
keywords = "skeletal dysplasia, spondyloepimetaphyseal dysplasia, UFSP2 gene",
author = "{Di Rocco}, M. and M. Rusmini and F. Caroli and A. Madeo and M. Bertamino and G. Marre-Brunenghi and I. Ceccherini",
year = "2018",
month = "3",
day = "1",
doi = "10.1111/cge.13134",
language = "English",
volume = "93",
pages = "671--674",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "3",

}

TY - JOUR

T1 - Novel spondyloepimetaphyseal dysplasia due to UFSP2 gene mutation

AU - Di Rocco, M.

AU - Rusmini, M.

AU - Caroli, F.

AU - Madeo, A.

AU - Bertamino, M.

AU - Marre-Brunenghi, G.

AU - Ceccherini, I.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Beukes hip dysplasia is an autosomal dominant disease which has to date been described only in a large South African family of Dutch origin. The patients presented with progressive epiphyseal dysplasia limited to femoral capital epiphysis and their height was not significantly reduced. A unique variant of the ubiquitin-fold modifier 1 (Ufm1)-specific peptidase 2 (UFSP2) gene (c.868T>C) has been reported in all individuals from Beukes family with clinical and radiological diagnosis of Beukes hip dysplasia. Three individuals, propositus, mother, and grandmother, presented with short stature, joint pain, genu vara and a novel spondyloepimetaphyseal dysplasia involving epiphyses predominantly at hips, but also at knees, ankles, wrists and hands, associated with variable degrees of metaphysis and spine involvement. Exome sequencing allowed us to identify the heterozygous variant c.1277A>C of the UFSP2 gene, leading to the missense change p.D426A, in all 3 patients. This mutation is predicted as damaging and, similarly to the mutation originally described in the Beukes family (p. Y290H), directly affects one of the catalytic residues participating in the active site of the protein. This supports the novel notion that loss of catalytic UFSP2 activity, observed in association with different mutants and already experimentally proven in vitro, may have different clinical outcomes.

AB - Beukes hip dysplasia is an autosomal dominant disease which has to date been described only in a large South African family of Dutch origin. The patients presented with progressive epiphyseal dysplasia limited to femoral capital epiphysis and their height was not significantly reduced. A unique variant of the ubiquitin-fold modifier 1 (Ufm1)-specific peptidase 2 (UFSP2) gene (c.868T>C) has been reported in all individuals from Beukes family with clinical and radiological diagnosis of Beukes hip dysplasia. Three individuals, propositus, mother, and grandmother, presented with short stature, joint pain, genu vara and a novel spondyloepimetaphyseal dysplasia involving epiphyses predominantly at hips, but also at knees, ankles, wrists and hands, associated with variable degrees of metaphysis and spine involvement. Exome sequencing allowed us to identify the heterozygous variant c.1277A>C of the UFSP2 gene, leading to the missense change p.D426A, in all 3 patients. This mutation is predicted as damaging and, similarly to the mutation originally described in the Beukes family (p. Y290H), directly affects one of the catalytic residues participating in the active site of the protein. This supports the novel notion that loss of catalytic UFSP2 activity, observed in association with different mutants and already experimentally proven in vitro, may have different clinical outcomes.

KW - skeletal dysplasia

KW - spondyloepimetaphyseal dysplasia

KW - UFSP2 gene

UR - http://www.scopus.com/inward/record.url?scp=85040600426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040600426&partnerID=8YFLogxK

U2 - 10.1111/cge.13134

DO - 10.1111/cge.13134

M3 - Article

AN - SCOPUS:85040600426

VL - 93

SP - 671

EP - 674

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 3

ER -