61 319

Cited 25 times in

PAPSS2 mutations cause autosomal recessive brachyolmia

Authors
Miyake, N; Elcioglu, NH; Iida, A; Isguven, P; Dai, J; Murakami, N; Takamura, K; Cho, TJ; Kim, OH; Hasegawa, T; Nagai, T; Ohashi, H; Nishimura, G; Matsumoto, N; Ikegawa, S
Citation
Journal of medical genetics, 49(8):533-538, 2012
Journal Title
Journal of medical genetics
ISSN
0022-25931468-6244
Abstract
BACKGROUND: Brachyolmia is a heterogeneous group of skeletal dysplasias that primarily affects the spine. Clinical and genetic heterogeneity have been reported; at least three types of brachyolmia are known. TRPV4 mutations have been identified in an autosomal dominant form of brachyolmia; however, disease genes for autosomal recessive (AR) forms remain totally unknown. We conducted a study on a Turkish family with an AR brachyolmia, with the aim of identifying a disease gene for AR brachyolmia.



METHODS AND RESULTS: We examined three affected individuals of the family using exon capture followed by next generation sequencing and identified its disease gene, PAPSS2 (phosphoadenosine-phosphosulfate synthetase 2). The patients had a homozygous loss of function mutation, c.337_338insG (p.A113GfsX18). We further examined three patients with similar brachyolmia phenotypes (two Japanese and a Korean) and also identified loss of function mutations in PAPSS2; one patient was homozygous for IVS3+2delT, and the other two were compound heterozygotes for c.616-634del19 (p.V206SfsX9) and c.1309-1310delAG (p.R437GfsX19), and c.480_481insCGTA (p.K161RfsX6) and c.661delA (p.I221SfsX40), respectively. The six patients had short-trunk short stature that became conspicuous during childhood with normal intelligence and facies. Their radiographic features included rectangular vertebral bodies with irregular endplates and narrow intervertebral discs, precocious calcification of rib cartilages, short femoral neck, and mildly shortened metacarpals. Spinal changes were very similar among the six patients; however, epiphyseal and metaphyseal changes of the tubular bones were variable.



CONCLUSIONS: We identified PAPSS2 as the disease gene for an AR brachyolmia. PAPSS2 mutations have produced a skeletal dysplasia family, with a gradation of phenotypes ranging from brachyolmia to spondylo-epi-metaphyseal dysplasia.
MeSH terms
Asian Continental Ancestry GroupCase-Control StudiesChildChild, PreschoolDNA Mutational AnalysisExonsFemale*Genes, RecessiveGenetic Heterogeneity*Genetic LociGenetic Predisposition to DiseaseGenetic TestingHeterozygoteHumansMultienzyme Complexes/*genetics*MutationOsteochondrodysplasias/ethnology/*genetics/pathology/radiographyPedigreePhenotypeSulfate Adenylyltransferase/*geneticsTRPV Cation Channels/geneticsTurkey
DOI
10.1136/jmedgenet-2012-101039
PMID
22791835
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Radiology
AJOU Authors
김, 옥화
Full Text Link
Files in This Item:
fulltext not available.txtDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse