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. 2014 Dec 20:15:141.
doi: 10.1186/s12881-014-0141-2.

Clinical and GAA gene mutation analysis in mainland Chinese patients with late-onset Pompe disease: identifying c.2238G > C as the most common mutation

Xiao Liu  1 , Zhaoxia Wang  2 , Weina Jin  3 , He Lv  4 , Wei Zhang  5 , Chengli Que  6 , Yu Huang  7 , Yun Yuan  8
Affiliations

Clinical and GAA gene mutation analysis in mainland Chinese patients with late-onset Pompe disease: identifying c.2238G > C as the most common mutation

Xiao Liu et al. BMC Med Genet. .

Abstract

Background: Pompe disease is an autosomal recessive lysosomal glycogen storage disorder that has been reported in different ethnic populations which carry different common mutations of the acid alpha-glucosidase (GAA) gene. The GAA mutation pattern in mainland Chinese patients with late-onset Pompe disease is still not well understood.

Methods: We presented the clinical and genetic characteristics of 27 mainland Chinese late-onset Pompe patients from 24 families.

Results: GAA mutation analysis revealed 26 different mutations, including 10 that were novel. The allelic frequency of c.2238G > C (p.W746C) was found to be 27.08% in this patient group. Respiratory dysfunction was diagnosed in 10 of 11 patients who underwent pulmonary function evaluation, although only four required ventilator support at night.

Conclusions: Our findings indicate that c.2238G > C (p.W746C) is the most common mutation in mainland Chinese late-onset Pompe patients, as observed in Taiwanese patients. The novel mutations identified in this study expand the genetic spectrum of late-onset Pompe disease, and the prevalence of respiratory dysfunction highlights the importance of monitoring pulmonary function in late-onset Pompe patients.

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Figures

Figure 1
Figure 1
Myopathological changes in Patient 2 (A and B), Patient 12 (C and D) and Patient 22 (E and F). H&E staining shows extensive vacuolation in many fibers in Patient 2 (A), but only a few vacuolar fibers in Patient 12 (C) and Patient 22 (E). Vacuolar fibers stained positive for glycogen with PAS (B, D and F).
Figure 2
Figure 2
GAA mutation spectrums in 27 Chinese late-onset Pompe patients. All described mutations are shown above (blue, UTR; purple, introns; orange, exons).
Figure 3
Figure 3
Exon 10 skipping in Patient 20. Muscle cDNA was amplified with the primers encompassing exon 9 and 10 that normally yield a 381-bp fragment. An additional 267-bp fragment was detected in Patient 20. The 114-bp difference is exactly the same with the size of exon 10.
Figure 4
Figure 4
Conservation of four novel missense mutations in different species.
See this image and copyright information in PMC

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