Osteopathia striata with cranial sclerosis owing to WTX gene defect.
Osteopathia striata with cranial sclerosis (OSCS) is an X-linked dominant condition marked by linear striations mainly affecting the metaphyseal region of the long bones and pelvis in combination with cranial sclerosis. Recently, the disease-causing gene was identified as the WTX gene (FAM123B), an inhibitor of WNT signaling. A correlation was suggested between the position of the mutation and male lethality. We performed genotype and phenotype studies using 18 patients from eight families with possible WTX gene defects and expanded the clinical spectrum of the affected females. All investigated families diagnosed with OSCS had WTX gene defects. One family had a WTX gene deletion; three of four point mutations were novel. The earlier reported WTX c.1072C>T was detected in four sporadic patients and appears to be a hotspot for mutations. Based on the nature of the mutation present in a surviving male patient, our data do not support the hypothesis raised by Jenkins et al. (2009) regarding a genotype-phenotype correlation for male lethality. The finding of a gene involved in WNT signaling as the cause of this sclerosing bone phenotype is not unexpected, but further functional studies are needed to explain the specific features. The WTX gene is mutated in different types of cancer, and it remains to be explained why osteopathia striata patients appear not to have an increased risk of cancer.
Perdu
Bram
B
Department of Medical Genetics, University and University Hospital of Antwerp, 2610 Antwerp, Belgium.
de Freitas
Fenna
F
Frints
Suzanne G M
SG
Schouten
Meyke
M
Schrander-Stumpel
Connie
C
Barbosa
Mafalda
M
Pinto-Basto
Jorge
J
Reis-Lima
Margarida
M
de Vernejoul
Marie-Christine
MC
Becker
Kristin
K
Freckmann
Marie-Louise
ML
Keymolen
Kathlijn
K
Haan
Eric
E
Savarirayan
Ravi
R
Koenig
Rainer
R
Zabel
Bernhard
B
Vanhoenacker
Filip M
FM
Van Hul
Wim
W
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000235:genetics; D001848:Bone Diseases, Developmental / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011859:Radiography; D012598:Sclerosis; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics*
C517118:AMER1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D025521:Tumor Suppressor Proteins