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Clinical and Radiographic Features of the Autosomal Recessive form of Brachyolmia Caused by PAPSS 2 Mutations
Author(s) -
Iida Aritoshi,
SimsekKiper Pelin Özlem,
Mizumoto Shuji,
Hoshino Touma,
Elcioglu Nursel,
Horemuzova Eva,
Geiberger Stefan,
Yesil Gozde,
Kayserili Hülya,
Utine Gülen Eda,
Boduroglu Koray,
Watanabe Shigehiko,
Ohashi Hirofumi,
Alanay Yasemin,
Sugahara Kazuyuki,
Nishimura Gen,
Ikegawa Shiro
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22377
Subject(s) - missense mutation , biology , genetics , dysplasia , loss function , phenotype , short stature , mutation , anatomy , gene , endocrinology
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 PAPSS 2 , the gene encoding PAPS (3′‐phosphoadenosine 5′‐phosphosulfate) synthase 2. To understand brachyolmia caused by PAPSS 2 mutations ( PAPSS 2‐ brachyolmia), we extended our PAPSS 2 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 PAPSS 2 ‐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. PAPSS 2‐ brachyolmia includes phenotypes of the conventional clinical concept of brachyolmia, the H obaek and T oledo types, and is associated with abnormal androgen metabolism.