Novel GALT variations and genetic spectrum in Turkish population with the correlation of genotype and phenotype.


Kalay I., Gulec C., Balcı M. C., Toksoy G., Gokcay G., Basaran S., ...More

Annals of human genetics, vol.87, no.6, pp.285-294, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 87 Issue: 6
  • Publication Date: 2023
  • Doi Number: 10.1111/ahg.12523
  • Journal Name: Annals of human genetics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, International Bibliography of Social Sciences, BIOSIS, CAB Abstracts, EMBASE, zbMATH
  • Page Numbers: pp.285-294
  • Keywords: Duarte variant, galactose, galactose 1-phosphate uridylyltransferase, Galactosemia, GALT gene, genotype–phenotype, inherited metabolic disease, Turkish cohort
  • Istanbul University Affiliated: Yes

Abstract

Classic galactosemia (OMIM#230400) is an autosomal recessive inborn error of carbohydrate metabolism caused by a deficiency of the galactose-1-phosphate-uridyl-transferase enzyme encoded by the GALT gene. Even though a galactose-restricted diet efficiently resolves the acute complications, it is insufficient to prevent long-term complications regarding speech defects, intellectual functioning, premature ovarian failure, cataract, hepatomegaly, dysarthria, ataxia, and tremor. Seventy-seven patients who were genetically diagnosed with classic galactosemia were included in this cohort. Identified novel variants were classified based on their predicted effect on the GALT function. Further, potential genotype–phenotype correlations were investigated via statistical analysis. In total, 18 different sequence variants were identified, including four novels (c.200delG/p.(Arg67Profs*19), c.533T>G/ p.(Met178Arg), c.708_709delGT/p.(Ser236Argfs*30), c.467C>A/p.(Ser156*)). Jaundice was the most common short-term finding with 80% (61/77). Even with early diagnosis, intellectual disability is encountered with 36% (27/74) of the long-term complications. Patients with biallelic missense variants have a significantly higher prevalence of cataracts (OR: 17.9). Longitudinal observations showed attenuation of cataracts and hepatomegaly. This study has shown the GALT variation spectrum of the Turkish population with a 30-year retrospective cohort, submitting a significant contribution to the genotype/phenotype correlation in galactosemia. This study also highlights the cost-effective importance of Sanger sequencing in the diagnosis of single-gene metabolic diseases.