SLC29A3 was selected as the candidate gene based on the patient's clinical manifestations, and all exons and flanking regions in the patient's genomic DNA were sequenced.
A homozygous splice mutation (c.300+1G>C) resulting in a frameshift and truncated protein (p.N101LfsX34) was identified. The patient had insulin-dependent diabetes, congenital deafness, short stature, hyperpigmented patches on the skin, dysmorphic features, cardiomegaly, arthrogryposis, hepatosplenomegaly, anaemia with erythroblastopenia, and an inflammatory syndrome with fever and arthritis; she also presented with a fibrotic mediastinal mass. These clinical features overlapped with pigmented hypertrichosis with insulin-dependent diabetes (PHID), H syndrome, Faisalabad histiocytosis and sinus histiocytosis with massive lymphadenopathy (SHML), all of which are also caused by SLC29A3 mutations.
This is the most severe case reported of SLC29A3 mutations with cumulative features of all these syndromes. This extreme severity coincides with the most N-terminal location of the truncation mutation, thereby affecting all alternative transcripts of the gene. This case report extends the clinical variability of homozygous SLC29A3 mutations that result in a spectrum of multisystemic manifestations.