ORIGINAL PAPER M. Kambouris á H. Banjar á I. Moggari á H. Nazer á M. Al-Hamed á B. F. Meyer Identi®cation of novel mutations in Arabs with cystic ®brosis and their impact on the cystic ®brosis transmembrane regulator mutation detection rate in Arab populations Received: 18 December 1998 / Accepted: 14 May 1999 Abstract The cystic ®brosis transmembrane regulator (CFTR) gene in Arab patients with cystic ®brosis (CF) (sweat chloride >60 mmol/l) from 61 unrelated families was screened for mutations in exons 3, 4, 5, 7, 10, 11, 16 and 19 and for mutations W1282X, N1303K and 3849 + 10kbC ® T. Eight novel mutations were identi®ed. These are: in exon 4: a) 425del42 (an in-frame 42 bp deletion that removes 14 amino acids and causes Gln 98 ® His at the point of deletion), b) 475G ® T (Glu 115 ® Stop) and c) 548A ® T (His 139 ® Leu); in intron 5, 711 + 1G ® A (splice site mutation); in exon 10, 1548delG (deletion of a ``G'' nucleotide causing a frameshift mutation that alters the amino acid sequence at residue 473 and results in translation termination at residue 526); in exon 11, a) 1729T ® C (Ph 533 E ® Leu) and b) 1811 + 2 (splice site mutation) and ®nally in exon 19, 3361A ® T (Lys 1177 ® Stop). All mutations were detected by heteroduplex analysis and identi®ed by sequencing. Of more than 850 known CFTR mutations, only 9 were encountered. The comparative frequencies of the most common mutations are: 1548delG> I123V  DF508  3120 + 1G ® A > H139L. Screening for these ®ve mutations identi®es 60% of the CF alleles in Arab populations. The novel mutation 1548delG is the most frequent (17%) among Arabs. Conclusion Novel Arab-speci®c mutations were identi®ed in the CFTR gene underlying cystic ®brosis. As a result of this study, the CFTR mutation detection rate among Arabs with cystic ®brosis is now comparable to that of other populations. Key words Cystic ®brosis transmembrane regulator á Arab population á Cystic ®brosis á Mutations Abbreviations CF cystic ®brosis á CTFR cystic ®brosis transmembrane regulator á MDE mutation detection enhancement Introduction Cystic ®brosis (CF) is the most common autosomal re- cessive disorder in Caucasians with an incidence of ap- proximately 1/2500 live births [25]. Aected patients manifest chronic sinopulmonary disease in association with Pseudomonas infection, pancreatic exocrine insuf- ®ciency, elevated sweat chloride concentrations and male infertility due to bilateral absence of the vas de- ferens [5, 25]. The disease is caused by alterations in the cystic ®brosis transmembrane conductance regulator (CFTR) which functions as a chloride channel and regulator of other channels in epithelial cells [25]. More than 850 pathogenic mutations in the CFTR gene have been identi®ed to date (CF mutation database, http:// www.genet.sickkids.on.ca/cftr-cgi-bin/Mutation Table). Eur J Pediatr (2000) 159: 303±309 Ó Springer-Verlag 2000 M. Kambouris (&) 1,2 á H. Banjar 1 á I. Moggari 1 á H. Nazer 1 M. Al-Hamed 1 á B. F. Meyer 1 1 King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia 2 Yale University School of Medicine, New Haven, CT, 06510, USA e-mail: marios.kambouris@yale.edu Tel.: +966-1-442-4178, Fax: +966-1-442-7858