We report a male fetus with a 6.8 Mb deletion on chromosome 7p22.1p22.3 at 16 weeks of gestation. The fetus presented a heart-hand syndrome with great artery malposition, bilateral radial ray deficiency, a single pelvic kidney, and growth retardation. This deletion involves a minimal deleted region for cardiac malformation and the RAC1 gene, previously described in limb anomalies in mice. This fetus is the third human case with limb defects and RAC1 deletion.
StollCDottBAlembikYRothMP. Associated malformations among infants with radial ray deficiency. Genet Couns Geneva Switz2013; 24(2): 223–234.
2.
Yi LiQNewbury-EcobRATerrettJAet al.Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat Genet1997; 15(1): 21–29.
3.
Koshiba-TakeuchiKTakeuchiJKArrudaEPet al.Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart. Nat Genet2006; 38(2): 175–183.
4.
NayakSSShuklaALewisLet al.Clinical utility of fetal autopsy and its impact on genetic counseling. Prenat Diagn2015; 35(7): 685–691.
5.
CaignecCLBocenoMSaugier-VeberPet al.Detection of genomic imbalances by array based comparative genomic hybridisation in fetuses with multiple malformations. J Med Genet2005; 42(2): 121.
6.
RichardsEGZaveriHPWolfVLKangSHLScottDA. Delineation of a less than 200 kb minimal deleted region for cardiac malformations on chromosome 7p22. Am J Med Genet A2011; 155A(7): 1729–1734.
7.
SpelemanFCraenMLeroyJ. De novo terminal deletion 7p22.1pter in a child without craniosynostosis. J Med Genet1989; 26(8): 528–532.
8.
GallegoCJGrantJMikhailFMBargerCRobinNH. Use of array comparative genome hybridization in orofacial clefting. J Craniofac Surg2010; 21(5): 1591–1594.
9.
Schömig-SpingerMSchmidMBrosiWGrimmT. Chromosome 7 short arm deletion, 7p21→pter. Hum Genet1986; 74(3): 323–325.
10.
VanzoRJMartinMMSdanoMRTetaKAggarwalVSouthST. SNX8: a candidate gene for 7p22 cardiac malformations including tetralogy of fallot. Am J Med Genet A2014; 164(2): 554–556.
11.
SilversidesCKLionelACCostainGet al.Rare copy number variations in adults with tetralogy of Fallot implicate novel risk gene pathways. PLoS Genet2012; 8(8): e1002843.
12.
Koyanagi-KatsutaRAkimitsuNHamamotoHArimitsuNHatanoTSekimizuK. Embryonic lethality of mutant mice deficient in the p116 gene. J Biochem2002; 131(6): 833–837.
13.
Rodriguez-BravoVMaciejowskiJCoronaJet al.Nuclear pores protect genome integrity by assembling a premitotic and Mad1-dependent anaphase inhibitor. Cell2014; 156(5): 1017–1031.
14.
LaiC-WChenH-LLinK-Yet al.FTSJ2, a heat shock-inducible mitochondrial protein, suppresses cell invasion and migration. PLoS One2014; 9(3): e90818.
15.
NissinkJWMBistaMBreedJet al.MTH1 substrate recognition—an example of specific promiscuity. PLoS One2016; 11(3): e0151154.
SuzukiDYamadaAAmanoTet al.Essential mesenchymal role of small GTPase Rac1 in interdigital programmed cell death during limb development. Dev Biol2009; 335(2): 396–406.
18.
WuXTuXJoengKSHiltonMJWilliamsDALongF. Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell2008; 133(2): 340–353.
19.
VergultSHoogeboomAJMBijlsmaEKet al.Complex genetics of radial ray deficiencies: screening of a cohort of 54 patients. Genet Med2013; 15(3): 195–202.
20.
ShamseldinHEAnaziSWakilSMet al.Novel copy number variants and major limb reduction malformation: report of three cases. Am J Med Genet A2016; 170(5): 1245–1250.
21.
SouthgateLMachadoRDSnapeKMet al.Gain-of-function mutations of ARHGAP31, a Cdc42/Rac1 GTPase regulator, cause syndromic cutis aplasia and limb anomalies. Am J Hum Genet2011; 88(5): 574–585.
22.
Pebrel-RichardCRouzadeCKemenySet al.Refinement of the critical region in a new 7p22.1 microduplication syndrome including craniofacial dysmorphism and speech delay. Am J Med Genet A2014; 164(11): 2964–2967.
23.
PreiksaitieneEKasnauskieneJCiuladaiteZTumieneBPatsalisPCKučinskasV. Clinical and molecular characterization of a second case of 7p22.1 microduplication. Am J Med Genet A2012; 158A(5): 1200–1203.
24.
RenduJSatreVTestardHet al.7p22.3 microdeletion disrupting SNX8 in a patient presenting with intellectual disability but no tetralogy of Fallot. Am J Med Genet A2014; 164(8): 2133–2135.
