Segregation analysis of idiopathic talipes equinovarus in a Texan population

Andrade, Mariza de; Barnholtz, Jill S.; Amos, Christopher I.; Lochmiller, CarolLynn; Scott, Allison M.; Risman, Marjorie; Hecht, Jacqueline

doi:10.1002/(sici)1096-8628(19980901)79:2<97::aid-ajmg4>3.0.co;2-k

Cited by 49 publications

(33 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is unknown if a single gene or multiple factors are involved. As previously noted, a number of investigators have proposed that idiopathic clubfoot has a genetic basis and is multifactorial in origin [2,5,7,8,26,34]. The association we found between increased internal hip rotation and idiopathic clubfoot suggests that the genetic basis of femoral and/or acetabular anteversion, which are the likely cause(s) for increased internal hip rotation, may play a role in the etiology of idiopathic clubfoot.…”

Section: Discussionsupporting

confidence: 69%

See 1 more Smart Citation

The Association between Idiopathic Clubfoot and Increased Internal Hip Rotation

Howlett

Mosca

Bjornson

2009

Clinical Orthopaedics &Amp; Related Research

View full text Add to dashboard Cite

Clinical observation suggests the coexistence of increased internal hip rotation in limbs with clubfoot, thereby providing an additional, and perhaps overlooked, site of deformity to account for an intoeing gait in these limbs. Furthermore, assuming a genetic basis exists for exaggerated femoral and/or acetabular anteversion, which are the possible cause(s) for increased internal hip rotation, this association could provide another key to the multifactorial etiology of clubfoot. We asked whether such an association exists and retrospectively reviewed 114 children (178 clubfeet). We then tested for an association between clubfoot and increased internal hip rotation. These rotational measurements were compared with published normative data on torsion in children. In cases of unilateral clubfoot, an additional analysis compared the rotational profiles of the affected and unaffected extremities.

show abstract

Section: Discussionsupporting

confidence: 69%

“…Clubfoot, the most common congenital deformity of the musculoskeletal system, is believed to be etiologically multifactorial [2,5,7,8,10,14,26,34]. This means it is the result of the interaction of several genes and, to some extent, environmental factors.…”

Section: Introductionmentioning

confidence: 99%

The Association between Idiopathic Clubfoot and Increased Internal Hip Rotation

Howlett

Mosca

Bjornson

2009

Clinical Orthopaedics &Amp; Related Research

View full text Add to dashboard Cite

show abstract

“…Earlier studies using complex segregation analyses suggested a single incompletely dominant disease gene with unmeasured factors contributing to incomplete penetrance [56,71]. In a different study, segregation analysis suggested a recessive mixed model [16], and a complex segregation analysis in Pacific and Maori people demonstrated a single dominant gene with 33% penetrance [11]. A polygenic threshold model was also supported by the finding of the Carter effect, in which females require a greater genetic load in order to inherit the disorder than males [42].…”

Section: Etiologymentioning

confidence: 99%

Update on Clubfoot: Etiology and Treatment

Dobbs

Gurnett²

2009

Clinical Orthopaedics &Amp; Related Research

264

260

View full text Add to dashboard Cite

“…In New Zealand Polynesian populations with a high incidence of talipes equinovarus, the best model of inheritance is autosomal dominant with a low penetrance (33%). 10 In other populations, regressive logistic models of complex segregation suggest a single major gene effect with autosomal recessive, 11 or autosomal dominant inheritance 12 and an additional effect (polygenetic or environmental factors) shared among siblings. 13 The genetic basis of talipes equinovarus is gradually being revealed.…”

Section: Introductionmentioning

confidence: 99%

Copy number analysis of 413 isolated talipes equinovarus patients suggests role for transcriptional regulators of early limb development

et al. 2012

View full text Add to dashboard Cite

Talipes equinovarus is one of the most common congenital musculoskeletal anomalies and has a worldwide incidence of 1 in 1000 births. A genetic predisposition to talipes equinovarus is evidenced by the high concordance rate in twin studies and the increased risk to first-degree relatives. Despite the frequency of isolated talipes equinovarus and the strong evidence of a genetic basis for the disorder, few causative genes have been identified. To identify rare and/or recurrent copy number variants, we performed a genome-wide screen for deletions and duplications in 413 isolated talipes equinovarus patients using the Affymetrix 6.0 array. Segregation analysis within families and gene expression in mouse E12.5 limb buds were used to determine the significance of copy number variants. We identified 74 rare, gene-containing copy number variants that were present in talipes equinovarus probands and not present in 759 controls or in the Database of Genomic Variants. The overall frequency of copy number variants was similar between talipes equinovarus patients compared with controls. Twelve rare copy number variants segregate with talipes equinovarus in multiplex pedigrees, and contain the developmentally expressed transcription factors and transcriptional regulators PITX1, TBX4, HOXC13, UTX, CHD (chromodomain protein)1, and RIPPLY2. Although our results do not support a major role for recurrent copy number variations in the etiology of isolated talipes equinovarus, they do suggest a role for genes involved in early embryonic patterning in some families that can now be tested with large-scale sequencing methods. INTRODUCTIONIsolated talipes equinovarus, also called clubfoot, is one of the most common serious congenital birth defects with an estimated birth prevalence of 1 per 1000 live births. 1 Talipes equinovarus consists of malalignment of the bones and joints of the foot and ankle, and is distinguished from positional foot anomalies because it is rigid and not passively correctable (Figure 1). Approximately 20% of talipes equinovarus cases are associated with chromosomal abnormalities, or known genetic syndromes 2,3 and it is a common component of several neurological disorders, including distal arthrogryposis, myotonic dystrophy, and myelomeningocele. Despite the frequency of talipes equinovarus in neurological disorders, no consistent neuromuscular abnormalities have been identified in isolated talipes equinovarus patients using muscle biopsy or electrophysiological examinations. [4][5][6][7] Most cases of clubfeet (80%) occur as isolated birth defects and are considered idiopathic. 8 Approximately 25% of patients with isolated talipes equinovarus report a family history of talipes equinovarus, suggesting a genetic basis for this disorder. 9 Twin studies also support a role for genetic factors, as identical twins have a 33% concordance rate for talipes

show abstract

Segregation analysis of idiopathic talipes equinovarus in a Texan population

Cited by 49 publications

References 6 publications

The Association between Idiopathic Clubfoot and Increased Internal Hip Rotation

The Association between Idiopathic Clubfoot and Increased Internal Hip Rotation

Update on Clubfoot: Etiology and Treatment

Copy number analysis of 413 isolated talipes equinovarus patients suggests role for transcriptional regulators of early limb development

Contact Info

Product

Resources

About