Two new patients with acromesomelic dysplasia, PRKG2 type-identification and characterization of the first missense variant

AKGÜN DOĞAN Ö., Diaz-Gonzalez F., de Lima Jorge A. A., Onenli-Mungan N., Menezes Andrade N. L., de Polli Cellin L., ...Daha Fazla

EUROPEAN JOURNAL OF HUMAN GENETICS, cilt.32, sa.10, ss.1250-1256, 2024 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 32 Sayı: 10
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1038/s41431-023-01472-z
  • Dergi Adı: EUROPEAN JOURNAL OF HUMAN GENETICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1250-1256
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Evet

Özet

Acromesomelic dysplasia, PRKG2 type (AMDP, MIM 619636), is an extremely rare autosomal recessive skeletal dysplasia characterized by severe disproportionate short stature presenting with acromesomelia, mild metaphyseal widening of the long bones and mild spondylar dysplasia. To date, only four variants have been reported; one nonsense, one splice-site, and two frameshifts in five AMDP families. Here, we report the first missense variant and a second splice-site variant in PRKG2 in two patients with clinical and radiological features of acromesomelic dysplasia. Furthermore, functional studies of the novel missense variant, p.Val470Gly, revealed that it was unable to down-regulate FGF2-induced MAPK signaling and, thus, would be predicted to cause growth delay. Hence, this report expands the mutational spectrum in skeletal dysplasias associated with PRKG2 variants. In addition, we propose recognizable facial features with acromesomelic dysplasia, PRKG2 type.