İlknur Erol , Şeyda Beşen, Elif Perihan Öncel, Leman Tekin Orgun, Sevcan Tug Bozdoğan

Objective The TRAPP(Transport protein particle) protein family consists of a complex group of proteins with many subunits which is mainly involved in membrane trafficking,autophagy and mitosis.Mutations in the TRAPPC6B gene have been described in 8 cases so far.The common features of the cases are global developmental delay,microcephaly,epilepsy,brain atrophy,autistic findings and early onset generalized epilepsy. Methods The first two Turkish patients with TRAPPC6B mutation-related global developmental delay,autistic findings,and corpus callosum thinning are discussed in this study. Case1 The proband was presented with developmental delay at the age of 22 months.His family history was remarkable with a cousin marriage and developmental delay in one of his sisters and cousins. Gait disturbance was found throughout his physical and neurological assessment along with minor dysmorphic findings. Significant developmental delay was detected. The neuroimagining revealed volume loss in the white matter,thinning of the corpus callosum and periventricular millimetric calcifications on the left side.The patient was initially tested for interferonopathies,but no mutations were identified.Whole exome analysis revealed a homozygous mutation c.32A>G pH11R (NM001079537.1)in the TRAPPC6B gene. Case2 A homozygous mutation in the TRAPPC6B gene was encountered in a TRAPPC6B gene sequencing that was performed since the index case's 5-year-old sister had a similar history.It was confirmed that both the mother and father were carriers. Conclusion The siblings expanded the spectrum of TRAPPC6B gene-related neurodegenerative diseases by demonstrating a phenotype of global developmental delay, intellectual disability, severe speech delay, and periventricular millimetric calcifications without any seizures and microcephaly.

Keywords: TRAPPC6B,calcifications,microcephaly,global developmental delay

İlknur Erol
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey

Şeyda Beşen
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey

Elif Perihan Öncel
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey

Leman Tekin Orgun
Baskent University Faculty of Medicine, Adana Dr. Turgut Noyan Application and Research Center
Turkey

Sevcan Tug Bozdoğan
Cukurova University AGENTEM (Adana Genetic Diseases Diagnosis and Treatment Center) and Medical Genetics Department of Medical Faculty
Turkey