A New Mutation in IDS Gene Causing Hunter Syndrome: A Case Report

Abstract

Rationale: Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked multisystem disorder, caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase (I2S). The clinical manifestations of this disease are severe skeletal deformities, airway obstruction, cardiomyopathy, and neurologic deterioration.

Patient: The patient was 5 years and 6 months boy, with developmental delay, hearing loss, hepatosplenomegaly, and skeletal dysplasia. He was diagnosed with mucopolysaccharidosis type II based on clinical manifestations, biochemical and genetic analysis.

Outcomes: The patient carries a new mutation (c.879-1210_1007-218del) in hemizygosis in the IDS gene, which was defined as pathogenic according to the 2015 American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines and as responsible for the mucopolysaccharidosis type II phenotype in the patient.

Keywords: Hunter syndrome; IDS; iduronate-2-sulfatase; inborn errors of metabolism; lisossomal storage disease; mucopolysaccharidosis type II.

Figure 1

Patient's dysmorphic facial features—broad nasal bridge, large rounded cheeks, and thick large lips.

Figure 2

Patient's radiographic findings. (A) Proximal pointed phalanges of hands. (B) Proximal pointed phalanges of feet. (C) Widened anterior and tapered posterior ribs (arrow). (D) “Beaked vertebra” of lumbar spine (arrow).

Figure 3

(A) IDS gene molecular structure. The red arrows show the breakpoints of the deletion observed in the patient (4,335 bp). (B) Electrophoresis of a long range PCR, showing the amplified fragment spanning from exon 6 to 8 (Fragment size: normal control 9,801 bp and patient 5,466 bp). (C) Sequence obtained from the genomic DNA of the patient shows the junction between intron 6 and 7 of the IDS gene (total deletion of exon 7).

Figure 4

Reverse transcriptase (RT) for IDS gene from total blood RNA obtained from the patient and his mother. (A) PCR fragment from exons 1–9 (expected fragment size 1,775 bp). It is possible to observe the generation of the fragments lacking exons 7 and 8 (1,474 bp) and fragment lacking exons 5, 7, and 8 (1,273 bp). (B) PCR fragment from exons 6 to 9 (expected fragment size 593 bp). It is possible to observe the generation of the fragments lacking exon 7 (466 bp) and fragment lacking exons 7 and 8 (292 bp). The figure depicts the transcript of 1,474 bp lacking exons 7 and 8 (C) and the transcript of 1,273 bp lacking exons 5, 7, and 8 (D).