Jacquinet Adeline, Brown Lindsay, Sawkins Jessica, Liu Pengfei, Pugash Denise, Van Allen Margot I, Patel Millan S
Department of Medical Genetics, University of British Columbia, Vancouver, Canada; Center for Human Genetics, Centre Hospitalier Universitaire and University of Liège, Liège, Belgium.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
Eur J Med Genet. 2018 May;61(5):257-261. doi: 10.1016/j.ejmg.2017.12.011. Epub 2017 Dec 24.
Fanconi anemia is a rare chromosome instability disorder with a highly variable phenotype. In the antenatal and neonatal periods, the diagnosis is usually suggested by the presence of typical congenital abnormalities such as intrauterine growth retardation, microcephaly and radial ray defects. We report a newborn female with a prenatal diagnosis of Fanconi anemia, complementation group O (FANCO). Antenatal ultrasounds identified symmetrical intrauterine growth retardation, complex heart defect as well as brain anomalies, overlapping fingers and cleft lip and palate. Imperforate anus was detected after birth. Compound heterozygous RAD51C variants c. [571+5G > A]; [c.935G > A] were detected by prenatal whole exome sequencing and cellular hypersensitivity to DNA interstrand crosslinking agents (DEB, MMC) was confirmed after birth. With only one previously described homozygous RAD51C variant to date, our findings expand the phenotypic spectrum of FANCO and suggest it should be part of the antenatal differential diagnosis for trisomy 13 and 18, due to the presence of atypical findings such as cleft lip and palate, holoprosencephaly, growth restriction and overlapping fingers.
范可尼贫血是一种罕见的染色体不稳定疾病，具有高度可变的表型。在产前和新生儿期，通常通过典型先天性异常的存在来提示诊断，如宫内生长迟缓、小头畸形和桡骨射线缺陷。我们报告了一名产前诊断为范可尼贫血O互补组（FANCO）的新生女婴。产前超声检查发现对称的宫内生长迟缓、复杂心脏缺陷以及脑异常、手指重叠、唇腭裂。出生后发现肛门闭锁。通过产前全外显子组测序检测到复合杂合RAD51C变异c. [571+5G > A]; [c.935G > A]，出生后证实对DNA链间交联剂（DEB、MMC）细胞超敏。由于存在唇腭裂、前脑无裂畸形、生长受限和手指重叠等非典型表现，迄今为止仅有一例先前描述的纯合RAD51C变异，我们的发现扩展了FANCO的表型谱，并提示其应作为13三体和18三体产前鉴别诊断的一部分。
