title: Adult phenotype and further phenotypic variability in SRD5A3-CDG.
abstract: BACKGROUND
  SRD5A3 is responsible for SRD5A3-CDG, a type of congenital disorder of glycosylation, and mutations have been reported in 15 children. All the mutations are recessive and truncating.
  
  
  METHODS
  We present 2 brothers at the age of 38 and 40 years with an initial diagnosis of cerebellar ataxia. We found the candidate disease loci via linkage analysis using data from single nucleotide polymorphism genome scans and homozygous truncating mutation SRD5A3 p.W19X, which was previously reported in 3 unrelated children, by exome sequencing.Clinical investigations included physical and ocular examinations and blood tests. Severe ocular involvement with retinal bone spicule pigmentation and optic atrophy are the most prominent disabling clinical features of the disease. The serum transferrin isoelectric focusing (TIEF) pattern is abnormal in the patient investigated.
  
  
  CONCLUSIONS
  Our patients are older, with later onset and milder clinical phenotypes than all patients with SRD5A3-CDG reported so far. They also have atypical ocular findings and variable phenotypes. Our findings widen the spectrum of phenotypes resulting from SRD5A3 mutations and the clinical variability of SRD5A3-CDG, and suggest screening for SRD5A3 mutations in new patients with at least a few of the clinical symptoms of SRD5A3-CDG.
authors.forename: Bülent
authors.initials: B
authors.lastname: Kara
authors.forename: Özgecan
authors.initials: Ö
authors.lastname: Ayhan
authors.forename: Gülden
authors.initials: G
authors.lastname: Gökçay
authors.forename: Nurdan
authors.initials: N
authors.lastname: Başboğaoğlu
authors.affiliation: Department of Molecular Biology and Genetics, Boğaziçi University, Istanbul, Turkey. tolun@boun.edu.tr.
authors.forename: Aslıhan
authors.initials: A
authors.lastname: Tolun
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000328:Adult; D018981:Congenital Disorders of Glycosylation / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D035781:Siblings
chemical_list: D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548469:SRD5A3 protein, human