| RRC ID |
44507
|
| 著者 |
Iida A, Simsek-Kiper PÖ, Mizumoto S, Hoshino T, Elcioglu N, Horemuzova E, Geiberger S, Yesil G, Kayserili H, Utine GE, Boduroglu K, Watanabe S, Ohashi H, Alanay Y, Sugahara K, Nishimura G, Ikegawa S.
|
| タイトル |
Clinical and radiographic features of the autosomal recessive form of brachyolmia caused by PAPSS2 mutations.
|
| ジャーナル |
Hum Mutat
|
| Abstract |
Brachyolmia is a heterogeneous skeletal dysplasia characterized by generalized platyspondyly without significant long-bone abnormalities. Based on the mode of inheritance and radiographic features, at least three types of brachyolmia have been postulated. We recently identified 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. To understand brachyolmia caused by PAPSS2 mutations (PAPSS2-brachyolmia), we extended our PAPSS2 mutation analysis to 13 patients from 10 families and identified homozygous or compound heterozygous mutations in all. Nine different mutations were found: three splice donor-site mutations, three missense mutations, and three insertion or deletion mutations within coding regions. In vitro enzyme assays showed that the missense mutations were also loss-of-function mutations. Phenotypic characteristics of PAPSS2-brachyolmia include short-trunk short stature, normal intelligence and facies, spinal deformity, and broad proximal interphalangeal joints. Radiographic features include platyspondyly with rectangular vertebral bodies and irregular end plates, broad ilia, metaphyseal changes of the proximal femur, including short femoral neck and striation, and dysplasia of the short tubular bones. PAPSS2-brachyolmia includes phenotypes of the conventional clinical concept of brachyolmia, the Hobaek and Toledo types, and is associated with abnormal androgen metabolism.
|
| 巻・号 |
34(10)
|
| ページ |
1381-6
|
| 公開日 |
2013-10-1
|
| DOI |
10.1002/humu.22377
|
| PMID |
23824674
|
| MeSH |
Child, Preschool
Consanguinity
Enzyme Activation
Exons
Female
Genes, Recessive*
Heterozygote
Homozygote
Humans
Introns
Male
Multienzyme Complexes / genetics*
Multienzyme Complexes / metabolism
Mutation*
Mutation, Missense
Osteochondrodysplasias / diagnostic imaging*
Osteochondrodysplasias / genetics*
Osteochondrodysplasias / metabolism
Phenotype
Radiography
Sulfate Adenylyltransferase / genetics*
Sulfate Adenylyltransferase / metabolism
|
| IF |
4.124
|
| 引用数 |
19
|
|
WOS 分野
|
GENETICS & HEREDITY
|
| リソース情報 |
| ヒト・動物細胞 |
|
