Akademik Veri Yönetim Sistemi
15. Ulusal Tıbbi Genetik Kongresi, Muğla, Türkiye, 9 - 13 Kasım 2022, ss.272
Background: FAM111A is a DNA-binding serine protease, composed of a PCNA-interacting box and a C-terminal trypsin‐like peptidase domain. FAM111A initiates S-phase entry by loading PCNA onto chromatin,1 and shows protease activity in excision of DNA-protein crosslinks (DPCs) from replication forks.2 FAM111A gain-of-function is associated with autosomal dominant Kenny-Caffey syndrome type 2 (KCS2), mainly characterized by short stature, skeletal abnormalities, dysmorphic facial features, and recurrent hypocalcemia due to hypoparathyroidism.3 Methods: We retrospectively evaluated clinical and molecular data of four patients with a clinical diagnosis of KCS2, from unrelated families originating from different regions of Turkey. The diagnosis was molecularly ascertained by direct sequencing of FAM111A and whole exome sequencing in one patient. Parental segregation analyses were performed in three families. Longitudinal follow-up data and growth parameters were collected. Results: All four patients displayed short stature, delayed closure of the anterior fontanel, characteristic facial features including prominent forehead and deeply set eyes, hypoparathyrodism and recurrent hypocalcemia. Less consistent facial features were upslanted and/or short palpebral fissures, depressed nasal bridge and tip. One patient presented cardiac and renal anomalies, in the form of atrial septal defect with pulmonary stenosis, and renal hypoplasia, respectively. One patient had borderline to mild intellectual deficit. Molecular analyses showed heterozygous FAM111A c.1706G>A; p.(Arg569His) in three patients, and novel, heterozygous c.928A>C; p.(lle310Leu) in one. In all, except one patient with c.1706G>A, parental analyses indicated de novo occurrence. Conclusion: We report two new patients with KCS2, and present follow-up data from two others that were previously presented in national congresses4,5. We also expand the mutational spectrum of FAM111A with the novel Ile310Leu variant. Clinical features of the cohort are consistent with those of previously patients with KCS2, including the patient harboring the novel variant. Three patients from different regions of Turkey with the Arg569His variant underline the pathogenicity and mutational hotspot characteristic of this residue.