Filges Isabel, Bruder Elisabeth, Brandal Kristin, Meier Stephanie, Undlien Dag Erik, Waage Trine Rygvold, Hoesli Irene, Schubach Max, de Beer Tjaart, Sheng Ying, Hoeller Sylvia, Schulzke Sven, Røsby Oddveig, Miny Peter, Tercanli Sevgi, Oppedal Truls, Meyer Peter, Selmer Kaja Kristine, Strømme Petter
Medical Genetics, University Hospital Basel, Basel, Switzerland.
Pathology, University Hospital Basel, Basel, Switzerland.
Hum Mutat. 2016 Apr;37(4):359-63. doi: 10.1002/humu.22960. Epub 2016 Feb 9.
Strømme syndrome was first described by Strømme et al. (1993) in siblings presenting with "apple peel" type intestinal atresia, ocular anomalies and microcephaly. The etiology remains unknown to date. We describe the long-term clinical follow-up data for the original pair of siblings as well as two previously unreported siblings with a severe phenotype overlapping that of the Strømme syndrome including fetal autopsy results. Using family-based whole-exome sequencing, we identified truncating mutations in the centrosome gene CENPF in the two nonconsanguineous Caucasian sibling pairs. Compound heterozygous inheritance was confirmed in both families. Recently, mutations in this gene were shown to cause a fetal lethal phenotype, the phenotype and functional data being compatible with a human ciliopathy [Waters et al., 2015]. We show for the first time that Strømme syndrome is an autosomal-recessive disease caused by mutations in CENPF that can result in a wide phenotypic spectrum.
斯特勒姆综合征最早由斯特勒姆等人（1993年）在患有“苹果皮”型肠闭锁、眼部异常和小头畸形的同胞中描述。其病因至今仍不明。我们描述了最初那对同胞以及另外两名先前未报道的同胞的长期临床随访数据，这两名同胞具有与斯特勒姆综合征重叠的严重表型，包括胎儿尸检结果。通过基于家系的全外显子组测序，我们在两对非近亲的白种人同胞对中鉴定出中心体基因CENPF中的截短突变。在两个家系中均证实为复合杂合遗传。最近，该基因的突变被证明会导致胎儿致死表型，其表型和功能数据与人类纤毛病相符[沃特斯等人，2015年]。我们首次表明，斯特勒姆综合征是一种由CENPF突变引起的常染色体隐性疾病，可导致广泛的表型谱。
