Cerebral creatine deficiency syndrome with a novel missense variant in SLC6A8 gene
Küçük Resim Yok
Tarih
2023
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wiley
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Cerebral creatine deficiency syndromes (CCDS) are three metabolic diseases characterized by loss of function in three proteins (GATM, GAMT, and SLC6A8) that required in creatine (Cr) synthesis pathway and transport. In this study, we aimed to identify the causal variant in a male who was 12-year-old manifesting intellectual disability (ID), seizures, expressive dysphasia and autism-like behavior. Urinary Cr metabolite measurements and MRI-spectroscopy (MRS) findings were consistent with CCDS. Molecular analysis revealed de novo hemizygous SLC6A8 (NM_005629.4): c.1400 T > G (p.Met467Arg) variant. The variant was not found in ClinVar, (the date of access: April 23th, 2023) and population databases (ExAC, gnomAD, 1000 Genomes, ESP 6500, Turkish Variome, GenomeAsia, Iranome, GME Variome, TOPMed Bravo and 4.7KJPN), it alters the physicochemical properties of the amino acid, the region is moderately conserved across species and in-silico prediction tools (REVEL, CADD, SIFT, PolyPhen2, Mutation Taster, MetaLR, MCAP, MetaRNN and MutPred) unanimously emphasize pathogenicity. Based on this evidence, the variant was interpreted as likely pathogenic according to the ACMG criteria (PS2, PM2,PP3, and PP4-S). This report may further elucidate the nature and phenotypic consequences of SLC6A8 variants.
Açıklama
Anahtar Kelimeler
Creatine, Epilepsy, Intellectual Disability
Kaynak
Neurology And Clinical Neuroscience
WoS Q Değeri
Scopus Q Değeri
Q4
Cilt
11
Sayı
5
