The role of biochemical testing in cystic fibrosis

@#Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder as a result of CF transmembrane conductance regulator gene mutation. It has a wide range of disease severity in patients with the same genotype. Case report: A 5-year-old Malay boy with a history of recurrent pneumonia, presented with productive cough, fever and worsening tachypnoea. Physical examination revealed coarse crepitations, reduced breath sounds and clubbing. Biochemical investigations showed that he had respiratory type 2 failure as a result of bronchiectasis. Sweat conductivity done twice was raised supporting a diagnosis of CF. Other investigations such as bronchoscopy to look for congenital anomaly of the lung, infectious disease screening and tuberculosis, fungal and viral culture and sensitivity were negative. Further cascade screening revealed high sweat conductivity results in his siblings. Discussion: Although CF prevalence is low in Malaysia, it is nevertheless an important diagnosis to be recognised as it is associated with increased morbidity.

Cystic fibrosis transmembrane conductance regulator (CFTR) gene abnormalities in Indian males with congenital bilateral absence of vas deferens & renal anomalies.

Background & objectives: The role of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in congenital bilateral absence of vas deferens and unilateral renal agenesis (CBAVD-URA) has been controversial. Here, we report the cases of five Indian males with CBAVD-URA. The objective was to evaluate the presence or absence of CFTR gene mutations and variants in CBAVD-URA. The female partners of these males were also screened for cystic fibrosis (CF) carrier status. Methods: Direct DNA sequencing of CFTR gene was carried out in five Indian infertile males having CBAVD-URA. Female partners (n=5) and healthy controls (n=32) were also screened. Results: Three potential regulatory CFTR gene variants (c.1540A>G, c.2694T>G and c.4521G>A) were detected along with IVS8-5T mutation in three infertile males with CBAVD-URA. Five novel CFTR gene variants (c.621+91A>G, c.2752+106A>T, c.2751+85_88delTA, c.3120+529InsC and c.4375-69C>T), four potential regulatory CFTR gene variants (M470V, T854T, P1290P, Q1463Q) and seven previously reported CFTR gene variants (c.196+12T>C, c.875+40A>G, c.3041-71G>C, c.3271+42A>T, c.3272-93T>C, c.3500-140A>C and c.3601-65C>A) were detected in infertile men having CBAVD and renal anomalies Interpretation & conclusions: Based on our findings, we speculate that CBAVD-URA may also be attributed to CFTR gene mutations and can be considered as CFTR-related disorder (CFTR-RD). The CFTR gene mutation screening may be offered to CBAVD-URA men and their female partners undergoing ICSI. Further studies need to be done in a large sample to confirm the findings.