Genetic study of eight Egyptian patients with pycnodysostosis: identification of novel CTSK mutations and founder effect.

Autor: Otaify GA; Clinical Genetics Department, Human Genetics and Genome Research Division, Center of Excellence for Human Genetics, National Research Centre, Cairo, Egypt. ghadaotaify@yahoo.com., Abdel-Hamid MS; Medical Molecular Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt., Mehrez MI; Orodental Genetics Department, Human Genetics and Genome Research Division, Center of Excellence for Human Genetics, National Research Centre, Cairo, Egypt., Aboul-Ezz E; Dental Basic Science Department, Dental and Oral Research Division, National Research Centre, Cairo, Egypt., Zaki MS; Clinical Genetics Department, Human Genetics and Genome Research Division, Center of Excellence for Human Genetics, National Research Centre, Cairo, Egypt., Aglan MS; Clinical Genetics Department, Human Genetics and Genome Research Division, Center of Excellence for Human Genetics, National Research Centre, Cairo, Egypt., Temtamy SA; Clinical Genetics Department, Human Genetics and Genome Research Division, Center of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA [Osteoporos Int] 2018 Aug; Vol. 29 (8), pp. 1833-1841. Date of Electronic Publication: 2018 May 23.
DOI: 10.1007/s00198-018-4555-0
Abstrakt: This is the first Egyptian study with detailed clinical and orodental evaluation of eight patients with pycnodysostosis and identification of four mutations in CTSK gene with two novel ones and a founder effect.
Introduction: Pycnodysostosis is a rare autosomal recessive skeletal dysplasia due to mutations in the CTSK gene encoding for cathepsin K, a lysosomal cysteine protease.
Methods: We report on the clinical, orodental, radiological, and molecular findings of eight patients, from seven unrelated Egyptian families with pycnodysostosis.
Results: All patients were offspring of consanguineous parents and presented with the typical clinical picture of the disorder including short stature, delayed closure of fontanels, hypoplastic premaxilla, obtuse mandibular angle, and drum stick terminal phalanges with dysplastic nails. Their radiological findings showed increased bone density, acro-osteolysis, and open cranial sutures. Mutational analysis of CTSK gene revealed four distinct homozygous missense mutations including two novel ones, c.164A>C (p. K55T) and c.433G>A (p.V145M). The c.164A>C (p. K55T) mutation was recurrent in three unrelated patients who also shared similar haplotype, suggesting a founder effect.
Conclusion: Our findings expand the mutational spectrum of CTSK gene and emphasize the importance of full clinical examination of all body systems including thorough orodental evaluation in patients with pycnodysostosis.
Databáze: MEDLINE
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