Familial microduplication of 17q23.1–q23.2 involving TBX4 is associated with congenital clubfoot and reduced penetrance in females. Am J Med Genet A 2014 Feb;164A(2):364-9
Date
03/05/2014Pubmed ID
24592505DOI
10.1002/ajmg.a.36238Scopus ID
2-s2.0-84892859035 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
Congenital clubfoot is a heterogeneous disorder that can result in functional disability, deformity, and pain if left untreated. Although the etiology is considered multifactorial in the majority of cases, a 17q23.1–q23.2 duplication has been reported in families with congenital clubfoot characterized by variable expressivity and incomplete penetrance. The candidate gene within the duplicated region is TBX4, a T-box transcription factor required for normal hind limb development. We describe a familial 2.15 Mb duplication in the 17q23.1–q23.2 region identified in a mother, daughter, and two sons. The male proband was referred for genetic evaluation due to multiple congenital anomalies including bilateral clubfoot, dysplastic hips, multiple heart defects, microcephaly, midfacial hypoplasia, brain anomalies on MRI scan, seizure disorder, optic nerve hypoplasia, hearing loss, and bilateral vocal cord paralysis. Cytogenetic testing on family members identified the 17q23.1–q23.2 duplication in both older siblings and the mother. In this family both male siblings had clubfoot, while females were phenotypically normal. Although TBX4 remains the candidate gene for congenital clubfoot involving 17q23.1–q23.2 duplications, the explanation for variable expressivity and penetrance remains unknown.
Author List
Peterson JF, Ghaloul-Gonzalez L, Madan-Khetarpal S, Hartman J, Surti U, Rajkovic A, Yatsenko SAMESH terms used to index this publication - Major topics in bold
Abnormalities, MultipleChromosome Duplication
Chromosomes, Human, Pair 17
Clubfoot
Comparative Genomic Hybridization
Female
Humans
Infant, Newborn
Male
Pedigree
Penetrance
Phenotype
T-Box Domain Proteins