CLINICAL AND GENETIC ASPECTS IN CDG

ASTEGGIANO, C.G.(1,2,3); PAPAZOGLU, G.M.(1,2); DODELSON DE KREMER; R.; NG, B. G; FREEZE, H.H.

Guanajuato

Congreso; 3ER CONGRESO LATINOAMERICANO DE GLICOBIOLOGIA; 2015

Sociedad Latinoamericana de Glicobiolgía

Introduction: Congenital Disorders of Glycosylation (CDG) are human geneticdiseases due to defects in attachment of glycans to proteins, lipids andproteoglycans in the lumen of the endoplasmic reticulum (ER) and their elaborationin the Golgi apparatus. The clinical features range from a severe multisystem tomild phenotype and are often associated with neurological impairments.Objective: To identify gene alterations in CDG-x Latin American patients.Methodology: Serum transferrin (Tf) was analyzed by Isoelectric Focusing (IEF),High Performance Liquid Chromatography (HPLC) and Mass Spectrometry (MS).Sanger sequencing and Whole Exome Sequence (WES), were carried out todetect the affected gene. Results: A multisystem clinical phenotype was observedin six patients with CDG-I or CDG-II glycosylation patterns. We detected twoPMM2-CDG patients and two ALG2-CDG siblings by exome sequencing andconfirmed by Sanger sequencing. We also identified COL6A2 mutations in apatient with CDG-II pattern, with autosomal recessive myosclerosis myopathy,rather than a CDG disease. One CDG-IIx patient requires further analysis.Conclusion: PMM2-CDG, the most frequent CDG, leads to the loss ofphosphomannomutase 2 activity and presented clinical features highly variable(from a multisystem stage to a severe neurological presentation). ALG2-CDG, arare form of CDG, was reported only in one patient deficient in alpha 1,3mannosyltransferase presenting refractory epilepsy, maturation and mentalretardation, severe hypotonia, facial dysmorphia, weak tendon reflexes andhypsarrhythmia. Five from six Argentinean CDG-x patients carried mutations ingenes that alter glycosylation pathway. We highlight the Next GenerationSequence method to detect genes involved in CDG. SupportedCONICET/FONCYT/UCC/Sanford-Burnham.