Mosaicism of the UDP-Galactose transporter SLC35A2 in a female causing a congenital disorder of glycosylation: a case report

Abstract

BackgroundCongenital disorders of glycosylation are rare conditions caused by genetic defects in glycan synthesis, processing or transport. Most congenital disorders of glycosylation involve defects in the formation or transfer of the lipid-linked oligosaccharide precursor of N-linked glycans. SLC35A2-CDG (previously CDG-IIm) is caused by hemizygous or heterozygous mutations in the X-linked gene SLC35A2 that encodes a UDP-galactose transporter. To date there have only been 10 reported patients with SLC35A2 mutations. Importantly, the patient presented here was not identified in infancy by transferrin isoform analysis, the most common testing to identify patients with a congenital disorder of glycosylation.Case presentationA 27 month old girl with developmental delay, central hypotonia, cerebral atrophy, and failure to thrive with growth retardation was identified by whole exome sequencing to have a mosaic missense variant in SLC35A2 (c.991G > A). This particular variant has been previously reported in a male as a mutation. Comparison of all clinical findings and new information on growth pattern, growth hormone testing and neurodevelopmental evaluation are detailed on the patient presented.ConclusionThis patient report increases the clinical and scientific knowledge of SLC35A2-CDG, a rare condition. New information on reduced growth, growth hormone sufficiency, lack of seizures, and neurodevelopmental status are presented. This new information will be helpful to clinicians caring for individuals with SLC35A2-CDG. This report also alerts clinicians that transferrin isoform measurements do not identify all patients with congenital disorders of glycosylation.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0617-6) contains supplementary material, which is available to authorized users.

Clinical, neuroradiological, and biochemical features of SLC35A2‐CDG patients

“…For comparison, there are at least eight patients described previously as detailed case reports and six patients (including patients 5 and 8 in our cohort) from larger cohort studies, where patients were studied with WES for different purposes . Recently, the clinical data of seven new female patients was published . Interestingly, the majority of the reported patients are females, and this was also seen in our cohort.…”

SLC35A2‐CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals

“…Sanger sequencing confirmed the presence of a de novo c.698 T > C (p.Leu233Pro) change (Table ). In total, 26/30 (87%) were de novo variants not previously reported, while a few were recurrent de novo variants p.Arg55Pro, p.Gln168Ter, p.Ala253Glyfs*100, and p.Val331Ile (Euro, Epilepsy Phenome/Genome, & Epi, ; Ng et al, ; Sim et al, ; Westenfield et al, ; Winawer et al, ; Table and Figure ). CDG‐0468 carried the c.502 C > T (p.Gln168Ter) and was part of the Epi4K study mentioned above.…”

“…The majority of previously reported SLC35A2‐CDG individuals, 27 of 32 (84%; Table S1), were identified by NGS with many of those affected individuals listed in the online supplemental data of large sequencing studies (Bosch et al, ; Bruneel et al, ; Dorre et al, ; Euro, Epilepsy Phenome/Genome, & Epi, ; Kimizu et al, ; Kodera et al, ; Lelieveld et al, ; Ng et al, ; Sim et al, ; Westenfield et al, ; Winawer et al, ; Yates et al, ). This explains why the number of reported subjects cited varies among studies.…”

“…To date, molecular and clinical information on 32 individuals with de novo variants in SLC35A2 have been reported with most exhibiting neurological symptoms, especially epilepsy, developmental delay, and intellectual disability (Bosch et al, ; Bruneel et al, ; Dorre et al, ; Euro, Epilepsy Phenome/Genome, & Epi, ; Kimizu et al, ; Kodera et al, ; Lelieveld et al, ; Ng et al, ; Sim et al, ; Westenfield et al, ; Winawer et al, ; Yates et al, ). Recently, WES analysis of brain specimens from 56 individuals identified five subjects harboring somatic de novo SLC35A2 variants (Winawer et al, ).…”

The Financial Impact of Genetic Diseases in a Pediatric Accountable Care Organization

“…Genetic disorders collectively encompass Mendelian (single gene) diseases, chromosomal abnormalities, birth defects, or other congenital anomalies. To date, there are 6000+ known genetic disorders cataloged in Online Mendelian Inheritance in Man (15). The number of diseases with a known genetic component is rapidly increasing through the advancement of genetic research and breakthrough of sequencing technologies (16)(17)(18).…”