Dataset Information

Identification of a novel LMX1B nonsense variant associated with congenital talipes equinovarus by prenatal exome sequencing: A case report.

ABSTRACT:

Background

Congenital talipes equinovarus (CTEV) is a rotational foot deformity that affects muscles, bones, connective tissue, and vascular or neurological tissues. The etiology of CTEV is complex and unclear, involving genetic and environmental factors. Nail-patella syndrome is an autosomal dominant disorder caused by variants of the LIM homeobox transcription factor 1 beta gene (LMX1B, OMIM:602575). LMX1B plays a key role in the development of dorsal limb structures, the kidneys, and the eyes, and variants in this gene may manifest as hypoplastic or absent patella, dystrophic nails, and elbow and iliac horn dysplasia; glomerulopathy; and adult-onset glaucoma, respectively. This study aimed to identify pathogenic variants in a fetus with isolated talipes equinovarus diagnosed by ultrasound in the second trimester, whose father exhibited dysplastic nails and congenital absence of bilateral patella.

Methods

Prenatal whole-exome sequencing (WES) of the fetus and parents was performed to identify the genetic variant responsible for the fetal ultrasound abnormality, followed by validation using Sanger sequencing.

Results

A novel heterozygous nonsense variant in exon 6 of LMX1B (c.844C>T, p.Gln282*) was identified in the fetus and the affected father but was not detected in any unaffected family members. This nonsense variant resulted in a premature termination codon at position 282, which may be responsible for the clinical phenotype through the loss of function of the gene product.

Conclusions

Our study indicating that a fetus carrying a novel nonsense variant of LMX1B (c.844C>T, p.Gln282*) can exhibit isolated talipes equinovarus, which expands the LMX1B genotypic spectrum and is advantageous for genetic counseling.

SUBMITTER: Chen J

PROVIDER: S-EPMC10767578 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Identification of a novel LMX1B nonsense variant associated with congenital talipes equinovarus by prenatal exome sequencing: A case report.

Chen Jing J Xiang Qinqin Q Xiao Xiao X Xu Bocheng B Xie Hanbing H Wang He H Yang Mei M Liu Shanling S

Molecular genetics & genomic medicine 20231106 1

<h4>Background</h4>Congenital talipes equinovarus (CTEV) is a rotational foot deformity that affects muscles, bones, connective tissue, and vascular or neurological tissues. The etiology of CTEV is complex and unclear, involving genetic and environmental factors. Nail-patella syndrome is an autosomal dominant disorder caused by variants of the LIM homeobox transcription factor 1 beta gene (LMX1B, OMIM:602575). LMX1B plays a key role in the development of dorsal limb structures, the kidneys, and ...[more]

PMID: 37930140

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Project description:BackgroundTreatment of idiopathic congenital talipes equinovarus (CTEV) is challenging for pediatric orthopedic surgeons. The Ponseti method is an effective protocol for treatment due to its technique of manipulation, casting, and limited surgery. Plaster casting is an essential component of the Ponseti method. In this report, we describe a new brace that was developed for use in the treatment of clubfoot in newborns instead of a plaster cast.MethodsThis retrospective study was performed in two orthopedic medical centers. Between January 2011 and October 2013, 89 newborns with CTEV (131 ft) underwent corrective treatment using fixation braces in the experiment group (E-group) in our hospital, and 107 newborns with CTEV (141 ft) underwent plaster casting in the control group (C-group) in another medical center. All patients were treated according to the Ponseti method after the application of the inclusion and exclusion criteria. Plaster casts were applied to patients in the C-group. The patients in the E-group received the custom-made polyaxial fixation braces instead of plaster casts. Prospective follow-up was performed for a mean duration of 36 months. The efficacy of the treatment was assessed using Pirani's scoring system. Chi-squared and independent t tests were used for statistical analyses.ResultsIn the E-group, 85 patients (125 ft) achieved good appearance within 3 months of treatment initiation (average, 1.7 months). Four patients (6 ft) required percutaneous Achilles tenotomy. Seven patients developed sores during treatment because of improper brace application, but all sores healed without scarring with timely treatment. In the C-group, 96 patients (123 ft) achieved good appearance within 3 months of treatment initiation (average, 1.6 months). Eleven patients (18 ft) required percutaneous Achilles tenotomy. Twenty-one feet developed sores during treatment because of plaster cast pressure on the dorsum of the feet. Sixteen sores healed without scarring with timely treatment, and 5 ft had obvious scars. The overall mean Pirani scores 1 year after treatment were 0.26 ± 0.06 in the E-group and 0.25 ± 0.03 in the C-group, and the Pirani scores 3 years after treatment were 0.23 ± 0.05 in the E-group and 0.22 ± 0.03 in the C-group. There were significant differences in the percutaneous Achilles tenotomy and skin sores but no significant difference in the Pirani scores between these two groups.ConclusionsOur results showed that the new polyaxial fixation brace used in this study was an effective tool for the corrective treatment of CTEV in newborns. We propose the use of this brace as an alternative treatment for newborns.

Project description:BackgroundIdiopathic congenital talipes equinovarus (CTEV) is the commonest form of clubfoot. Its exact cause is unknown, although it is related to limb development. The aim of this study was to quantify the anatomy of the muscle, subcutaneous fat, tibia, fibula and arteries in the lower legs of teenagers and young adults with CTEV using 3D magnetic resonance imaging (MRI), and thus to investigate the anatomical differences between CTEV participants and controls.Methodology/principal findingsThe lower legs of six CTEV (2 bilateral, 4 unilateral) and five control young adults (age 12-28) were imaged using a 3T MRI Philips scanner. 5 of the CTEV participants had undergone soft-tissue and capsular release surgery. 3D T1-weighted and 3D magnetic resonance angiography (MRA) images were acquired. Segmentation software was used for volumetric, anatomical and image analysis. Kolmogorov-Smirnov tests were performed. The volumes of the lower affected leg, muscle, tibia and fibula in unilateral CTEV participants were consistently smaller compared to their contralateral unaffected leg, this was most pronounced in muscle. The proportion of muscle in affected CTEV legs was significantly reduced compared with control and unaffected CTEV legs, whilst proportion of muscular fat increased. No spatial abnormalities in the location or branching of arteries were detected, but hypoplastic anomalies were observed.Conclusions/significanceCombining 3D MRI and MRA is effective for quantitatively characterizing CTEV anatomy. Reduction in leg muscle volume appears to be a sensitive marker. Since 5/6 CTEV cases had soft-tissue surgery, further work is required to confirm that the treatment did not affect the MRI features observed. We propose that the proportion of muscle and intra-muscular fat within the lower leg could provide a valuable addition to current clinical CTEV classification. These measures could be useful for clinical care and guiding treatment pathways, as well as treatment research and clinical audit.

Dataset Information

Identification of a novel LMX1B nonsense variant associated with congenital talipes equinovarus by prenatal exome sequencing: A case report.

Background

Methods

Results

Conclusions

Publications

Identification of a novel LMX1B nonsense variant associated with congenital talipes equinovarus by prenatal exome sequencing: A case report.

Similar Datasets

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