A case of mucolipidosis II presenting with prenatal skeletal dysplasia and severe secondary hyperparathyroidism at birth

Heo, Ju Sun; Choi, Ka Young; Sohn, Se Hyoung; Kim, Curie; Kim, Yoon Joo; Shin, Seung Han; Lee, Jae Myung; Lee, Juyoung; Sohn, Jin A; Lim, Byung Chan; Lee, Jin A; Choi, Chang Won; Kim, Ee-Kyung; Kim, Han-Suk; Kim, Beyong Il; Choi, Jung-Hwan

GNPTAB, which is the only gene known to be associated with ML II, was first identified by Tiede et al. 30) in 2005. ML II correlates with an almost total absence of phosphotransferase activity resulting from homozygosity or compound heterozygosity due to frameshift or nonsense mutations in the GNPTAB gene. However, the presence of at least 1 hypomorph (a missense or splicing site mutation) allele in the GNPTAB mutant genotype results in a clinically milder form of ML III alpha/beta with a low level of phosphotransferase activity 3) . The same result was reported in a Korean study 26) . We performed a genetic study by direct sequencing of all coding exons and flanking intronic regions of GNPTAB. We identified compound heterozygosity in the GNPTAB gene: a combination of a nonsense mutation (c.3091C>T [p.Arg1031X]) and a frameshift by a small insertion or duplication (c.3456_3459dupCAAC [p.Ile1154GlnfsX3]). We confirmed the diagnosis as ML II because the hypomorph allele was not present. The nonsense mutation was inherited from the father, and the frameshift mutation was inherited from the mother. The c.3091C>T mutation has been noted in the literature 3) , but the c.3456_3459dupCAAC mutation is novel.