A mutation in KIF7 is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance
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Published:2012-05-15
Issue:1
Volume:7
Page:
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ISSN:1750-1172
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Container-title:Orphanet Journal of Rare Diseases
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language:en
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Short-container-title:Orphanet J Rare Dis
Author:
Ali Bassam R,Silhavy Jennifer L,Akawi Nadia A,Gleeson Joseph G,Al-Gazali Lihadh
Abstract
Abstract
Background
We previously reported the existence of a unique autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance mapping to chromosome 15q26.
Methods
In this manuscript, we have used whole exome sequencing on two affected members of a consanguineous family with this condition and carried out detailed bioinformatics analysis to elucidate the causative mutation.
Results
Our analysis resulted in the identification of a homozygous p.N1060S missense mutation in a highly conserved residue in KIF7, a regulator of Hedgehog signaling that has been recently found to be causing Joubert syndrome, fetal hydrolethalus and acrocallosal syndromes. The phenotype in our patients partially overlaps with the phenotypes associated with those syndromes but they also exhibit some distinctive features including multiple epiphyseal dysplasia.
Conclusions
We report the first missense homozygous disease-causing mutation in KIF7 and expand the clinical spectrum associated with mutations in this gene to include multiple epiphyseal dysplasia. The missense nature of the mutation might account for the unique presentation in our patients.
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Genetics (clinical),General Medicine
Reference24 articles.
1. Lachman RS, Krakow D, Cohn DH, Rimoin DL: MED, COMP, multilayered and NEIN: an overview of multiple epiphyseal dysplasia. Pediatr Radiol. 2005, 35 (2): 116-123. 10.1007/s00247-004-1323-4. 2. Unger S, Bonafé L, Superti-Furga A: Multiple epiphyseal dysplasia: clinical and radiographic features, differential diagnosis and molecular basis. Best Pract Res Clin Rheumatol. 2008, 22 (1): 19-32. 10.1016/j.berh.2007.11.009. 3. Katoh Y, Katoh M: KIF27 is one of orthologs for Drosophila Costal-2. Int J Oncol. 2004, 25 (6): 1875-1880. 4. Cheung HO, Zhang X, Ribeiro A, Mo R, Makino S, Puviindran V, Law KK, Briscoe J, Hui CC: The kinesin protein Kif7 is a critical regulator of Gli transcription factors in mammalian hedgehog signaling. Sci Signal. 2009, 2 (76): ra29-10.1126/scisignal.2000405. 5. Putoux A, Thomas S, Coene KL, Davis EE, Alanay Y, Ogur G, Uz E, Buzas D, Gomes C, Patrier S, Bennett CL, Elkhartoufi N, Frison MH, Rigonnot L, Joyé N, Pruvost S, Utine GE, Boduroglu K, Nitschke P, Fertitta L, Thauvin-Robinet C, Munnich A, Cormier-Daire V, Hennekam R, Colin E, Akarsu NA, Bole-Feysot C, Cagnard N, Schmitt A, Goudin N, Lyonnet S, Encha-Razavi F, Siffroi JP, Winey M, Katsanis N, Gonzales M, Vekemans M, Beales PL, Attié-Bitach T: KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes. Nat Genet. 2011, 43 (6): 601-606. 10.1038/ng.826.
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