Identification of a Novel De Novo COMP Gene Variant as a Likely Cause of Pseudoachondroplasia

Tuncel G., Akcan N., Gul Ş., Sag S. O., Bundak R., Mocan G., ...Daha Fazla

APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY, cilt.29, sa.7, ss.546-550, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 29 Sayı: 7
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1097/pai.0000000000000914
  • Dergi Adı: APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.546-550
  • Anahtar Kelimeler: pseudoachondroplasia, COMP, PSACH, novel variant, rare disease, OLIGOMERIC MATRIX PROTEIN, MULTIPLE EPIPHYSEAL DYSPLASIA, CALCIUM-BINDING, MUTATION, COLLAGEN
  • İstanbul Üniversitesi Adresli: Evet

Özet

Next-generation sequencing technology and advanced sequence analysis techniques are markedly speeding up the identification of gene variants causing rare genetic diseases. Pseudoachondroplasia (PSACH, MIM 177170) is a rare disease inherited in an autosomal dominant manner. It is known that variations in the cartilage oligomeric matrix protein (COMP) gene are associated with the disease. Here, we report a 39-month-old boy with short stature. He gave visible growth and development delayed phenotype after 12 months. Further genetic resequencing analysis was carried out to identified the disease-causing variant. Furthermore, computational approaches were used to characterize the effect of the variant. In this study, we identify and report a novel variation in the COMP gene, c.1420_1422del (p.Asn47del), causing a spontaneous form of PSACH in our patient. Our in silico model indicated that any mutational changes in this region are very susceptible to PASCH phenotype. Overall, this study is the first PSACH case in the Turkish Cypriot population. Moreover, this finding contributes to the concept that the genotype-phenotype correlation in COMP is still unknown and also improves our understanding of this complex disorder.