A Chinese Pediatric cystic fibrosis patient with the
c.1624G>T, p. Gly542x / c.223C>T, p. Arg75x
genotype
To the Editor,
We read with great interest the article entitled “A systematic review
of the clinical and genetic characteristics of Chinese patients with
cystic fibrosis” by Ruihe Shi and colleagues (year 2020, volume 55,
issue 11). The authors reported that common CFTR gene mutations, such as
c.1624G>T, c.1652G>A, c.350G>A,
had not been reported in China [1].
Here, we report a case of a Chinese CF child with gene mutations of
1624G>T,
p. Gly542x (heterozygous mutation, paternal) and
c.223C>T,
p. Arg75x (heterozygous mutation, maternal) (Figure 1). This 5-year-old
female patient presented with chronic cough, expectoration, wheezing,
and growth retardation since the age of 3. Due to recurrent pulmonary
infection and repeated dyspnea, she was hospitalized approximately 2
times every year. During her first admission to our hospital when she
was 33-month-old, sputum culture was positive for Pseudomonas
aeruginosa. On the 9th day of hospitalization, she
suffered from abdominal distension and weakened bowel sounds, and
failure to pass flatus or bowel movements for 3 days without obvious
peritonitis. Abdominal CT showed that the colon was narrow, part of the
colon wall was thickened; liver density was generally decreased. The
surgery was performed given the diagnosis of Hirschsprung’s disease.
Human whole exome sequencing was conducted by Beijing Quanpu Medical
Laboratory on the 23rd day of admission. On
13th April 2022, during her third admission to our
hospital when she was 46-month-old due to aggravated cough and wheezing,
along with the gene mutations of 1624G>T, p. Gly542x and
c.223C>T, p. Arg75x, the diagnosis of cystic fibrosis was
made. Sputum and bronchoalveolar lavage fluid cultures were consistently
positive for Pseudomonas aeruginosa, aztreonam was administered for
anti-infection. Serum vitamin examination did not show lipo-soluble
vitamins deficiency at that time. Since inhaled tobramycin was not
available in our country, her discharge medications were oral cefixime,
azithromycin, and inhaled hypertonic saline.
During the most recent admission, she presented with malnutrition
(weight <25th centile) and chronic diarrhea. Serum vitamin
examination showed lipo-soluble vitamins deficiency, consequently, she
needed supplementation of lipo-soluble vitamins and pancreatic enzyme
replacement therapy. Increased secretions were seen under bronchoscopy.
Sputum culture was positive for both Staphylococcus aureus and
Pseudomonas aeruginosa, while bronchoalveolar lavage fluid culture was
only positive for Staphylococcus aureus. Linezolid plus
piperacillin-tazobactam were prescribed according to drug sensitivity
results for anti-bacterial treatment this time.
Mutations in CFTR, the gene encoding the epithelial ion channel that
normally transports chloride and bicarbonate, lead to impaired mucus
hydration and clearance [2]. Despite the high
morbidity in Caucasian, it is still a rare disease in China. At present,
about 200 CF patients have been reported in China, however, no
population-based prevalence was calculated [3].
Recent study revealed that the prevalence of Chinese CF ranged from
1/153,825 to 1/110,127 [4]. The most common CFTR
gene mutations in Chinese CF patients, which presented with c.2909G→A,
are different from those in Caucasian patients[1]. However, the child in our report carried a
common gene mutation among Caucasian patients but rare among Chinese
patients. By searching the CFTR2 database (http://www.cftr2.org), we
found that there were only 4 patients with this variant combination in
the CFTR2 database and this variant combination may able to cause
pancreatic insufficiency. She experienced colostomy due to neonatal
megacolon, and surgery for meconium ileus. Although her clinical
manifestations were typical for CF, without sufficient understanding of
this disease and newborn screening, the age at CF diagnosis is
relatively older. Sweat detection is an important and accurate method
for detecting CF,in which the chloride ion concentration is usually
higher than 60 mmol/L, however, we did not find an institution that
could perform this test during her first admission in our hospital.
The population-specific genetic spectrum of CF is still unknown, and CF
prevalence would be significantly underestimated in Chinese if using the
Caucasian-specific screening panel. Thus, recent study recommended the
53 pathogenic/likely-pathogenic variants as CF screening panel for
Chinese population, especially the six variants with high allele
frequencies: G970D (c.2909G>A), D979A
(c.2936A>C), M469V (c.1405A>G), G622D
(c.1865G>A), L88X (c.263T>G), and
1898+5G->T (c.1766+5G>T), which could also be
used in clinical diagnosis process [4]. Besides,
in a most recent systematic review of gene mutations of Chinese CF
patients, c.1624G>T was not reported as well[5]. To our knowledge, this is the first report of
c.1624G>T mutation among Chinese patients with CF and this
gene mutation would be a complementary for Chinese-specific screening
panel.
In conclusion, we present this case in order to complement CFTR gene
mutations data of Chinese children with cystic fibrosis and improve
clinicians’ understanding of this disease in China. Besides, with the
development of molecular biology technology, gene detection was expected
to play an important role in the early diagnosis, early treatment, and
prognosis improvement of the disease.