Cystic fibrosis with homozygous R553X mutation in a Taiwanese child

Abstract

It has been reported that cystic fibrosis is very rare in Asians, and its clinical expression and genetic mutations are different from those found in Caucasians. We report the case of a boy who had chronic diarrhea with failure to thrive and frequent respiratory tract infections beginning at the age of 2 months. He developed bronchiectasis with chronic severe hypoxemia and pancreatic insufficiency by the age of 3 years and 5 months, which raised the consideration of cystic fibrosis. DNA analysis revealed a homozygous R553X mutation, and both his parents were subsequently proven to be R553X carriers. This case is the first report in a Taiwanese with cystic fibrosis attributable to a mutation commonly seen in Caucasians. However, the age of onset was much younger and the clinical course was more severe than those associated with Western patients. We reviewed the eight reported Taiwanese patients with cystic fibrosis, including the present case. We believe that the incidence of cystic fibrosis in Taiwan may be underestimated. Both genetic and environmental factors may play a role in the phenotypic disparity between Asians and Caucasians.

Characterization of gene mutations and phenotypes of cystic fibrosis in Chinese patients

“…Based on the mutation frequencies, common and uncommon mutations were defined. In the present study, the most common mutation in Caucasians, F508del, was not detected; R553X, a much less common mutation accounting for 0.7% of CF patients in Caucasians, was present in patient 2. Q98R is a mutation that was first reported in Southern France and is primarily detected in Koreans and Japanese, with a detection rate as high as 18.8% .…”

“…However, CF has rarely been reported in Chinese patients, and there has been minimal CF research effort in China. To our knowledge, fewer than 30 patients have been reported in the Chinese population, and only 14 of them were reported as being from the Chinese mainland . In general, Chinese CF patients present with chronic airway infection, bronchiectasis, but with pancreatic sufficiency, which has made the diagnosis of CF less straightforward; the mutations detected in Chinese CF patients are rarely seen in the Caucasian population, as is evident from a literature review .…”

“…To our knowledge, fewer than 30 patients have been reported in the Chinese population, and only 14 of them were reported as being from the Chinese mainland . In general, Chinese CF patients present with chronic airway infection, bronchiectasis, but with pancreatic sufficiency, which has made the diagnosis of CF less straightforward; the mutations detected in Chinese CF patients are rarely seen in the Caucasian population, as is evident from a literature review . Although approximately 2000 CFTR gene mutations have been found in CF patients, as recorded by the Cystic Fibrosis Gene Analysis Consortium (CFGAC; http://www.genet.sickkids.on.ca/), only the 32 most frequent mutations are listed in the CFTR gene mutation screening bank, and sometimes, only 23 CFTR mutations are used in an initial screening test .…”

“…[3][4][5][6][7][8][9][10][11][12] In general, Chinese CF patients present with chronic airway infection, bronchiectasis, but with pancreatic sufficiency, which has made the diagnosis of CF less straightforward; the mutations detected in Chinese CF patients are rarely seen in the Caucasian population, as is evident from a literature review. [3][4][5][6][7][8][9][10][11][12] Although approximately 2000 CFTR gene mutations have been found in CF patients, as recorded by the Cystic Fibrosis Gene Analysis Consortium (CFGAC; www.genet.sickkids.on.ca/), only the 32 most frequent mutations are listed in the CFTR gene mutation screening bank, 1 and sometimes, only 23 CFTR mutations are used in an initial screening test. 13 The remainder are considered rare mutations and, in most countries, only looked for in those highly suspected patients who are negative for the common mutations.…”

Cystic fibrosis: A new mutation in the Lebanese population

“…Many reports have shown that pancreatic dysfunction is directly correlated with the CFTR genotype [16,17] as both our patients had chronic diarrhea and the younger sibling had cholestasis involved. Studies have shown that Asians had different gene expressivity and tend to exhibit phenotypes at an earlier age than Caucasians for the same genotype [18,19,20]. This was also suggested in Arab populations who reportedly presented more frequently with meconium ileus than the Caucasian populations for the ΔF508del mutation [5].…”