Cathepsin K analysis in a pycnodysostosis cohort: demographic, genotypic and phenotypic features

Orphanet Journal of Rare Diseases

Serap Turan²  Yasemin Alanay⁵  Koray Boduroglu³  Belma Haliloglu²  Teoman Akçay²  Zeynep Atay²  Behzat Özkan⁶  Tülay Güran²  Pelin Özlem Şimşek Kiper³  Ajda Coker⁴  Abdullah Bereket²  Ahmet Arman¹ 

[1] The Department of Medical Genetics, Marmara University, Istanbul, Turkey;The Department of Pediatric Endocrinology, Marmara University, İstanbul, Turkey;The Department of Pediatric Genetics, Hacettepe University, Ankara, Turkey;The Department of Molecular Biology and Genetics, Istanbul Kultur University, Istanbul, Turkey;Pediatric Genetics, Department of Pediatrics, Acibadem University School of Medicine, İstanbul, Turkey;Department of Pediatric Endocrinology, Medeniyet University, Istanbul, Turkey

关键词: Arnold Chiari malformation;    Craniosynostosis;    Fracture;    Pycnodysostosis;    Cathepsin K;   

Others  :  861959
DOI  :  10.1186/1750-1172-9-60

 received in 2013-12-16, accepted in 2014-04-14,  发布年份 2014

【 摘 要 】

Background

To characterize cathepsin K (CTSK) mutations in a group of patients with pycnodysostosis, who presented with either short stature or atypical fractures to pediatric endocrinology or dysmorphic features to pediatric genetics clinics.

Methods

Seven exons and exon/intron boundaries of CTSK gene for the children and their families were amplified with PCR and sequenced. Sixteen patients from 14 families with pycnodysostosis, presenting with typical dysmorphic features, short stature, frequent fractures and osteosclerosis, were included in the study.

Results

We identified five missense mutations (M1I, I249T, L7P, D80Y and D169N), one nonsense mutation (R312X) and one 301 bp insertion in intron 7, which is revealed as Alu sequence; among them, only L7P and I249 were described previously. The mutations were homozygous in all cases, and the families mostly originated from the region where consanguineous marriage rate is the highest. Patients with M1I mutation had fractures, at younger ages than the other pycnodysostosis cases in our cohort which were most probably related to the severity of mutation, since M1I initiates the translation, and mutation might lead to the complete absence of the protein. The typical finding of pycnodysostosis, acroosteolysis, could not be detected in two patients, although other patients carrying the same mutations had acroosteolysis. Additionally, none of the previously described hot spot mutations were seen in our cohort; indeed, L7P and R312X were the most frequently detected mutations.

Conclusions

We described a large cohort of pycnodysostosis patients with genetic and phenotypic features, and, first Alu sequence insertion in pycnodysostosis.

【 授权许可】

   
2014 Arman et al.; licensee BioMed Central Ltd.

【 图 表 】

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