Abstract:
BACKGROUND:Clubfoot is a common congenital birth defect with complex inheritance patterns. Currently, the genetic and morphological basis of clubfoot is poorly understood. To identify genetic risk factors associated with clubfoot, we performed a genome-wide association study of common genetic variants. METHODS:The DNA of 396 isolated clubfoot patients and 1000 controls of European descent was genotyped for >600 000 single nucleotide polymorphisms (SNP) using the Affymetrix 6.0 array. Replication was performed with an independent cohort of 370 isolated clubfoot cases and 363 controls of European descent. RESULTS:Strongest evidence for an association of clubfoot was found with an intergenic SNP on chromosome 12q24.31 between NCOR2 and ZNF664 (rs7969148, OR=0.58, p=1.25×10⁻⁵) that was significant on replication (combined OR=0.63, p=1.90×10⁻⁷). Additional suggestive SNPs were identified near FOXN3, SORCS1 and MMP7/TMEM123 that also confirmed on replication. CONCLUSIONS:Our study suggests a potential role for common genetic variation in several genes that have not previously been implicated in clubfoot pathogenesis.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Zhang TX,Haller G,Lin P,Alvarado DM,Hecht JT,Blanton SH,Stephens Richards B,Rice JP,Dobbs MB,Gurnett CAdoi
10.1136/jmedgenet-2014-102303subject
Has Abstractpub_date
2014-05-01 00:00:00pages
334-9issue
5eissn
0022-2593issn
1468-6244pii
jmedgenet-2014-102303journal_volume
51pub_type
杂志文章abstract::Mutations in genes involved in Ras signalling cause Noonan syndrome and other disorders characterised by growth disturbances and variable neuro-cardio-facio-cutaneous features. We describe two sisters, 46 and 31 years old, who presented with dysmorphic features, hypotonia, feeding difficulties, retarded growth and psy...
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