Identification of a novel compound heterozygous IDUA mutation underlies Mucopolysaccharidoses type I in a Chinese pedigree

Abstract Background Mucopolysaccharidosis type I (MPS I) is a rare autosomal storage disorder resulting from the defective alpha‐L‐iduronidase (encoded by IDUA) enzyme activity and accumulation of glycosaminoglycans (GAGs) in lysosomes. So far, more than 100 IDUA causative mutations have been identified leading to three MPS I phenotypic subtypes: Hurler syndrome (severe form), Hurler/Scheie syndrome (intermediate form), and Scheie syndrome (mild form). Methods Whole‐exome sequencing (WES) was performed to identify the underlying genetic mutations. To verify the identified variations, Sanger sequencing was performed for all available family members following PCR amplification. The impact on IDUA protein was analyzed by sequential analysis and homology modeling. Results A novel IDUA heterozygous single base insertion (c.1815dupT, p.V606Cfs51*) and a known missence mutation (c.T1037G, p.L346R) were detected in our patient diagnosed as congenital heart disease with heart valve abnormalities. The novel frameshift mutation results in a complete loss of 48 amino acids in the Ig‐like domain and causes the formation of a putative protein product which might affect the IDUA enzyme activity. Conclusions A novel compound heterozygous IDUA mutation (c.1815dupT, p.V606Cfs51*) was found in a Chinese MPS I family. The identification of the mutation facilitated accurate genetic counseling and precise medical intervention for MPS I in China.