Clinical and molecular study of Egyptian pediatric patients with Crigler-Najjar syndrome

Abstract Background Crigler-Najjar syndrome (CNS) is a rare autosomal recessive inherited disorder caused by uridine diphosphate-glucuronosyltransferase (UGT) enzyme deficiency. The enzyme is encoded by the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) gene. This study aims to examine the clinical and molecular characteristics of CNS in Egyptian child patients. Methods Twenty Egyptian Crigler-Najjar patients, 17 with CNS type 1 and 3 with CNS type 2, were subjected to a thorough history, clinical examination, and laboratory investigations. All patients and their parents had their UGT1A1 coding exons sequenced and their mutations analyzed. Results This study revealed two novel homozygous mutations located in exon 1, a missense (c.175 G > T, p.V59F), detected in nine patients representing 45% of the study cohort, and a single-nucleotide deletion at position c.300delT leading to a stop codon (F100Lfs*10) and premature termination of the encoded transcript. The c.300delT was detected in seven patients (35% of the cases). Another two previously reported, but very rare homozygous mutations, neither mentioned in ExAC nor 1000G, were identified in our Egyptian patients, and a pathogenic delAG in exon 1 at c.722_723delAG, E241Gfs*16, was detected in exon 1 in two patients (10% of cases) and a nonsense pathogenic nonsense mutation c.1448 G > A in exon 5 in two patients (10% of cases). Conclusion Sequencing the UGT1A1 gene in Egyptian patients with CNS types I and II has identified four mutations, three of which are located in exon 1, pointing out exon 1, probably as a hotspot in our cohort. Molecular testing of clinically suggested CNS cases is of valuable importance in proper management and genetic counseling of such cases and their families. This is the first CNS molecular screening study performed in Egypt.