Open Access Case report

Adult phenotype and further phenotypic variability in SRD5A3-CDG

Bülent Kara1, Özgecan Ayhan2, Gülden Gökçay3, Nurdan Başboğaoğlu4 and Aslıhan Tolun2*

Author Affiliations

1 Department of Pediatrics, Division of Child Neurology, Kocaeli University Medical Faculty, Kocaeli, Turkey

2 Department of Molecular Biology and Genetics, Boğaziçi University, Istanbul, Turkey

3 Department of Pediatrics, Division of Nutrition and Metabolism, Istanbul University Istanbul Medical Faculty, Istanbul, Turkey

4 Department of Ophthalmology, Düzce University Medical Faculty, Düzce, Turkey

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BMC Medical Genetics 2014, 15:10  doi:10.1186/1471-2350-15-10

Published: 16 January 2014

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.

Case presentation

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.

Conclusion

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.

Keywords:
SRD5A3; SRD5A3-CDG; CDG; Glycosylation defect