PCSK5 mutation in a patient with the VACTERL association
Tóm tắt
The VACTERL association is a typically sporadic, non-random collection of congenital anomalies that includes vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, renal anomalies, and limb abnormalities. Although several chromosomal aberrations and gene muta
tions have been reported as disease-causative, these findings have been sparsely replicated to date. In the present study, whole exome sequencing of a case with the VACTERL association uncovered a novel frameshift mutation in the PCSK5 gene, which has been reported as one of the causative genes for the VACTERL association. Although this mutation appears potentially pathogenic in its functional aspects, it was also carried by the healthy father. Furthermore, a database survey revealed several other deleterious variants in the PCSK5 gene in the general population. Further studies are necessary to clarify the etiological role of the PCSK5 mutation in the VACTERL association.
Tài liệu tham khảo
Solomon BD (2011) VACTERL/VATER Association. Orphanet J Rare Dis 6:56
Reardon W, Zhou XP, Eng C (2001) A novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association. J Med Genet 38:820e3
Garcia-Barceló MM, Wong KK, Lui VC, Yuan ZW, So MT, Ngan ES et al (2008) Identification of a HOXD13 mutation in a VACTERL patient. Am J Med Genet 146A:3181e5
Stankiewicz P, Sen P, Bhatt SS, Storer M, Xia Z, Bejjani BA et al (2009) Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations. Am J Hum Genet 84:780–791
Wessels MW, Kuchinka B, Heydanus R, Smit BJ, Dooijes D, de Krijger RR et al (2010) Polyalanine expansion in the ZIC3 gene leading to X- linked heterotaxy with VACTERL association: a new polyalanine dis- order? J Med Genet 47:351–355
McCauley J, Masand N, McGowan R, Rajagopalan S, Hunter A, Michaud JL et al (2011) X-linked VACTERL with hydrocephalus syndrome: further delineation of the phenotype caused by FANCB mutations. Am J Med Genet 155A:2370–2380
Saisawat P, Kohl S, Hilger AC, Hwang DY, Yung Gee H, Dworschak GC et al (2014) Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association. Kidney Int 85:1310–1317
Chung B, Shaffer LG, Keating S, Johnson J, Casey B, Chitayat D (2011) From VACTERL-H to heterotaxy: variable expressivity of ZIC3-related disorders. Am J Med Genet A 155A:1123–1128
Schramm C, Draaken M, Bartels E, Boemers TM, Aretz S, Brockschmidt FF et al (2011) De novo microduplication at 22q11.21 in a patient with VACTERL association. Eur J Med Genet 54:9–13
Hilger A, Schramm C, Pennimpede T, Wittler L, Dworschak GC, Bartels E et al (2013) De novo microduplications at 1q41, 2q37.3, and 8q24.3 in patients with VATER/VACTERL association. Eur J Hum Genet 21:1377–1382
Dworschak GC, Draaken M, Marcelis C, de Blaauw I, Pfundt R, van Rooij IA et al (2013) De novo 13q deletions in two patients with mild anorectal malformations as part of VATER/VACTERL and VATER/VACTERL-like association and analysis of EFNB2 in patients with anorectal malformations. Am J Med Genet A 161A:3035–3041
Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM et al (2010) Exome sequencing identifies the cause of a mendelian disorder. Nat Genet 42:30–35
Rabbani B, Tekin M, Mahdieh N (2014) The promise of whole-exome sequencing in medical genetics. J Hum Genet 59:5–15
Winberg J, Gustavsson P, Papadogiannakis N, Sahlin E, Bradley F, Nordenskjöld E et al (2014) Mutation Screening and Array Comparative Genomic Hybridization Using a 180 K Oligonucleotide Array in VACTERL Association. PLoS One 9:e85313
Szumska D, Pieles G, Essalmani R, Bilski M, Mesnard D, Kaur K et al (2008) VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5. Genes Dev 22:1465–1477
Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25:1754–1760
Flicek P, Amode MR, Barrell D, Beal K, Billis K, Brent S et al (2014) Ensembl 2014. Nucleic Acids Res 42 (Database issue): D749–D755
Cingolani P, Platts A, le Wang L, Coon M, Nguyen T, Wang L et al (2012) A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3”. Fly (Austin) 6:80–92
Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL (2012) Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinform 13:134
Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM et al (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29:308–311
1000 Genomes Project Consortium, Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM et al (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491:56–65
Zdobnov EM, Apweiler R (2001) InterProScan—an integration platform for the signature-recognition methods in InterPro. Bioinformatics 17:847–848
Constam DB, Calfon M, Robertson EJ (1996) SPC4, SPC6, and the novel protease SPC7 are coexpressed with bone morphogenetic proteins at distinct sites during embryogenesis. J Cell Biol 134:181–191
Rancourt SL, Rancourt DE (1997) Murine subtilisin-like proteinase SPC6 is expressed during embryonic implantation, somitogenesis, and skeletal formation. Dev Genet 21:75–81
Essalmani R, Zaid A, Marcinkiewicz J, Chamberland A, Pasquato A, Seidah NG et al (2008) In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate. Proc Natl Acad Sci USA 105:5750–5755
Essalmani R, Hamelin J, Marcinkiewicz J, Chamberland A, Mbikay M, Chrétien M et al (2006) Deletion of the gene encoding proprotein convertase 5/6 causes early embryonic lethality in the mouse. Mol Cell Biol 26:354–361
McPherron AC, Lawler AM, Lee SJ (1999) Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11. Nat Genet 22:260–264
Solomon BD (2011) VACTERL/VATER Association. Orphanet J Rare Dis. 16(6):56. doi:10.1186/1750-1172-6-56 (Review)
Wloga D, Rogowski K, Sharma N, Van Dijk J, Janke C, Eddé B et al (2008) Glutamylation on alpha-tubulin is not essential but affects the assembly and functions of a subset of microtubules in Tetrahymena thermophila. Eukaryot Cell 7:1362–1372
Kubo T, Yanagisawa HA, Yagi T, Hirono M, Kamiya R (2010) Tubulin polyglutamylation regulates axonemal motility by modulating activities of inner-arm dyneins. Curr Biol 20:441–445
