A novel association of campomelic dysplasia and hydrocephalus with an unbalanced chromosomal translocation upstream of SOX9

被引:7
作者
Antwi, Prince [1 ]
Hong, Christopher S. [1 ]
Duran, Daniel [1 ]
Jin, Sheng Chih [2 ]
Dong, Weilai [2 ]
DiLuna, Michael [1 ,3 ]
Kahle, Kristopher T. [1 ,3 ,4 ]
机构
[1] Yale Univ, Sch Med, Dept Neurosurg, 333 Cedar St, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA
[3] Yale Sch Med, Dept Pediat, New Haven, CT 06520 USA
[4] Yale Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1101/mcs.a002766
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Campomelic dysplasia is a rare skeletal dysplasia characterized by Pierre Robin sequence, craniofacial dysmorphism, shortening and angulation of long bones, tracheobronchomalacia, and occasionally sex reversal. The disease is due to mutations in SOX9 or chromosomal rearrangements involving the long arm of Chromosome 17 harboring the SOX9 locus. SOX9, a transcription factor, is indispensible in establishing and maintaining neural stem cells in the central nervous system. We present a patient with angulation of long bones and external female genitalia on prenatal ultrasound who was subsequently found to harbor the chromosomal abnormality 46, XY, t(6;17) (p21.1;q24.3) on prenatal genetic testing. Comparative genomic hybridization revealed deletions at 6p21.1 and 17q24.3, the latter being 2.3 Mb upstream of SOX9. Whole-exome sequencing did not identify pathogenic variants in SOX9, suggesting that the 17q24.3 deletion represents a translocation breakpoint farther upstream of SOX9 than previously identified. At 2 mo of age the patient developed progressive communicating ventriculomegaly and thinning of the cortical mantle without clinical signs of increased intracranial pressure. This case suggests ventriculomegaly in some cases represents not a primary impairment of cerebrospinal fluid dynamics, but an epiphenomenon driven by a genetic dysregulation of neural progenitor cell fate.
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页数:13
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