Abstract
Strømme syndrome is an ultra-rare primary ciliopathy with clinical variability. The syndrome is caused by bi-allelic variants in CENPF, a protein with key roles in both chromosomal segregation and ciliogenesis. We report three unrelated patients with Strømme syndrome and, using high-throughput sequencing approaches, we identified novel pathogenic variants in CENPF, including one structural variant, giving a genetic diagnosis to the patients. Patient 1 was a premature baby who died at 26 days with congenital malformations affecting many organs including the brain, eyes, and intestine. She was homozygous for a donor splice variant in CENPF, NM_016343.3:c.1068+1G>A, causing skipping of exon 7, resulting in a frameshift. Patient 2 was a female with intestinal atresia, microcephaly, and a Peters anomaly. She had normal developmental milestones at the age of 7 years. She is compound heterozygous for CENPF NM_016343.3:c.5920dup and c.8991del, both frameshift. Patient 3 was a male with anomalies of the brain, eye, intestine, and kidneys. He was compound heterozygous for CENPF p.(Glu298Ter), and a 5323 bp deletion covering exon 1. CENPF exon 1 is flanked by repetitive sequences that may represent a site of a recurrent structural variation, which should be a focus in patients with Strømme syndrome of unknown etiology.