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Computational and Structural... 2021Polydactyly is a highly heterogeneous group of skeletal deformities in clinical and genetic background. The variation spectrum in Chinese sporadic polydactyly has not...
PURPOSE
Polydactyly is a highly heterogeneous group of skeletal deformities in clinical and genetic background. The variation spectrum in Chinese sporadic polydactyly has not been comprehensively analyzed. To elucidate genetic variation spectrum and genotype-phenotype correlations in Chinese patients with polydactyly, we conducted comprehensive genetic analysis of patients nationwide using targeted sequencing.
METHODS
A total of 181 patients diagnosed with polydactylies were recruited. We designed a targeted capture panel for sequencing 721 genes that are associated with the pathogenesis of skeletal dysplasia. We performed rigorous variant- and gene-level filtrations to identify potentially damaging variants, followed by enrichment analysis and gene prioritization.
RESULTS
A total of 568 deleterious variants of 293 genes were identified in 173 of 181 patients with a positive rate of 95.6% by targeted sequencing. For each sample, an average of 3.17 deleterious variants were identified. Especially, 14 pathogenic or likely pathogenic variants were identified in 10 genes in 14 patients out of the 181 patients, providing a positive molecular diagnostic rate of 7.7%.
CONCLUSION
Targeted sequencing analysis provides a high efficiency approach for the genetic diagnosis of polydactyly. This is the largest next generation sequencing study performed to date in patients with polydactyly and represents the genetic basis of polydactyly typically encountered in genetics clinics.
PubMed: 34194672
DOI: 10.1016/j.csbj.2021.06.014 -
Taiwanese Journal of Obstetrics &... Nov 2022We present rapid confirmation of trisomy 13 of maternal origin by quantitative fluorescent polymerase chain reaction (QF-PCR) following postmortem tissue cell culture...
Rapid confirmation of trisomy 13 of maternal origin by QF-PCR following postmortem tissue cell culture failure in a pregnancy with trisomy 13 at amniocentesis and fetal postaxial polydactyly and facial cleft.
OBJECTIVE
We present rapid confirmation of trisomy 13 of maternal origin by quantitative fluorescent polymerase chain reaction (QF-PCR) following postmortem tissue cell culture failure in a pregnancy with trisomy 13 at amniocentesis and fetal postaxial polydactyly and facial cleft.
CASE REPORT
A 34-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX,+13. Prenatal ultrasound revealed postaxial polydactyly. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial cleft and postaxial polydactyly of the hand and foot. Postmortem cytogenetic analysis of the fetal tissue revealed no growth of the cells due to culture failure, but QF-PCR analysis on the DNA extracted from placenta, umbilical cord and parental bloods confirmed trisomy 13 and maternal origin of the extra chromosome 13.
CONCLUSION
QF-PCR analysis is useful for rapid perinatal confirmation of trisomy 13 and the parental origin of the extra chromosome 13, especially under the circumstance of tissue cell culture failure, and the acquired information is useful for genetic counseling.
Topics: Pregnancy; Female; Humans; Adult; Amniocentesis; Trisomy 13 Syndrome; Trisomy; Mosaicism; Comparative Genomic Hybridization; In Situ Hybridization, Fluorescence; Polydactyly; Fetus; Polymerase Chain Reaction; Cell Culture Techniques
PubMed: 36427972
DOI: 10.1016/j.tjog.2022.08.008 -
Journal of Applied Physiology... Jun 2003This review deals with the largest set of rat recombinant inbred (RI) strains and summarizes past and recent accomplishments with this platform for genetic mapping and... (Review)
Review
Genetic Models in Applied Physiology. HXB/BXH rat recombinant inbred strain platform: a newly enhanced tool for cardiovascular, behavioral, and developmental genetics and genomics.
This review deals with the largest set of rat recombinant inbred (RI) strains and summarizes past and recent accomplishments with this platform for genetic mapping and analyses of divergent and complex traits. This strain, derived by crossing the spontaneously hypertensive rat, SHR/Ola, with a Brown Norway congenic, BN-Lx, carrying polydactyly-luxate syndrome, is referred to as HXB/BXH. The RI strain set has been used for linkage and association studies to identify quantitative trait loci for numerous cardiovascular phenotypes, including arterial pressure, stress-elicited heart rate, and pressor response, and metabolic traits, including insulin resistance, dyslipidemia and glucose handling, and left ventricular hypertrophy. The strain's utility has been enhanced with development of a new framework marker-based map and strain distribution patterns of polymorphic markers. Quantitative trait loci for behavioral traits mapped include loci for startle motor response and habituation, anxiety and locomotion traits associated with elevated plus maze, and conditioned taste aversion. The polydactyly-luxate syndrome Lx mutation has allowed the study of alleles important to limb development and malformation phenotypes as well as teratogens. The RI strains have guided development of numerous congenic strains to test locus assignments and to study the effect of genetic background. Although these strains were originally developed to aid in studies of rat genetic hypertension and morphogenetic abnormalities, this rodent platform has been shown to be equally powerful for a wide spectrum of traits and endophenotypes. These strains provide a ready and available vehicle for many physiological and pharmacological studies.
Topics: Animals; Cardiovascular Physiological Phenomena; Chromosome Mapping; Fetus; Genetics; Genetics, Behavioral; Genomics; Polydactyly; Quantitative Trait Loci; Rats; Rats, Inbred BN; Rats, Inbred SHR; Recombination, Genetic
PubMed: 12736193
DOI: 10.1152/japplphysiol.00064.2003 -
PloS One 2018Macrodactyly is a congenital malformation characterized by aggressive overgrowth of multiple tissues, including subcutaneous fat, nerves, and bones in digits or limbs....
BACKGROUND
Macrodactyly is a congenital malformation characterized by aggressive overgrowth of multiple tissues, including subcutaneous fat, nerves, and bones in digits or limbs. In type II macrodactyly, the peripheral nerve is enlarged; however, the morphological and functional characteristics of the affected peripheral nerves have rarely been evaluated.
METHODS
In this research, six macrodactyly patients and three polydactyly patients (control) were studied. Pre-operative sensory nerve action potential and intra-operative nerve action potential tests were performed. The microstructure and ultrastructure of the enlarged nerves were observed and neurofilament (NF) expression was evaluated using immunofluorescent staining.
RESULTS
Axon impairment of the digital nerves originating from the median nerve (MN) was observed. A compensatory reinnervation from the ulnar nerve (UN) was found in two of the six patients, and significant morphological changes were observed in the enlarged nerve. The myelinated nerve fibers decreased, the lamellar structure of the myelin sheath changed, and the density of the NFs of the unmyelinated fibers decreased. There was aberrant distribution of NFs in the macrodactylous nerve tissues. In patients with compensatory UN reinnervation, the number of myelinated and unmyelinated fibers increased to normal levels; however, the diameter of the myelinated fibers apparently decreased.
CONCLUSIONS
The morphology and function of the macrodactylous enlarged nerve was impaired in type II macrodactyly patients; however, the unaffected UN partially compensated for the lost function of the affected MN under specific situations. Electrophysiological tests should be performed to determine the function of the affected nerve and surgical treatment for type II macrodactyly could be refined.
Topics: Action Potentials; Case-Control Studies; Electromyography; Hand Deformities, Congenital; Humans; Median Nerve; Peripheral Nerves; Polydactyly; Ulnar Nerve
PubMed: 30001338
DOI: 10.1371/journal.pone.0200183 -
International Journal of Molecular... May 2023Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy that affects multiple organs, leading to retinitis pigmentosa, polydactyly, obesity, renal anomalies,...
Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy that affects multiple organs, leading to retinitis pigmentosa, polydactyly, obesity, renal anomalies, cognitive impairment, and hypogonadism. Until now, biallelic pathogenic variants have been identified in at least 24 genes delineating the genetic heterogeneity of BBS. Among those, is a minor contributor to the mutation load and is one of the eight subunits forming the BBSome, a protein complex implied in protein trafficking within the cilia. This study reports on a European patient with a severe BBS phenotype. Genetic analysis was performed using multiple next-generation sequencing (NGS) tests (targeted exome, TES and whole exome, WES), and biallelic pathogenic variants could only be identified using whole-genome sequencing (WGS), including a previously missed large deletion of the first exons. Despite the absence of family samples, the biallelic status of the variants was confirmed. The BBS5 protein's impact was confirmed on the patient's cells (presence/absence and size of the cilium) and ciliary function (Sonic Hedgehog pathway). This study highlights the importance of WGS and the challenge of reliable structural variant detection in patients' genetic explorations as well as functional tests to assess a variant's pathogenicity.
Topics: Humans; Bardet-Biedl Syndrome; Cytoskeletal Proteins; Hedgehog Proteins; Mutation; Phenotype; Phosphate-Binding Proteins; Polydactyly; Protein Transport; Male; Child, Preschool
PubMed: 37240074
DOI: 10.3390/ijms24108729 -
Cell Death & Disease Jan 2021Mutations of WD40 repeat domain 60 (WDR60) have been identified in short-rib polydactyly syndromes (SRPS I-V), a group of lethal congenital disorders characterized by...
Mutations of WD40 repeat domain 60 (WDR60) have been identified in short-rib polydactyly syndromes (SRPS I-V), a group of lethal congenital disorders characterized by short ribs, polydactyly, and a range of extraskeletal phenotypes. However, the underlying mechanism is still unclear. Here, we report that WDR60 is essential for embryonic development and plays a critical role in the multipolar-bipolar transition and migration of newborn neurons during brain development. Mechanically, we found that WDR60 was located at the microtubule-organizing center to control microtubule organization and possibly, the trafficking of cellular components. Importantly, the migration defect caused by Wdr60 knockdown could be rescued by the stable form of α-Tubulin, α-Tubulin (an acetylation-mimicking mutant). These findings identified a non-cilia function of WDR60 and provided insight into its biological function, as well as the pathogenesis of WDR60 deficiency associated with SRPS.
Topics: Adaptor Proteins, Signal Transducing; Animals; Cell Movement; Female; Humans; Mice; Neurogenesis; Neurons; Rats; Short Rib-Polydactyly Syndrome
PubMed: 33436552
DOI: 10.1038/s41419-020-03363-3 -
Clinical Orthopaedics and Related... Jun 2017
Review
Topics: Humans; Orthopedic Procedures; Polydactyly; Predictive Value of Tests; Terminology as Topic; Thumb; Treatment Outcome
PubMed: 27613532
DOI: 10.1007/s11999-016-5068-9 -
PloS One 2017Polydactyly, a common heritable limb malformation in vertebrates, is characterized by supernumerary digits. In chickens, basic characteristics and rough dominant genes...
Polydactyly, a common heritable limb malformation in vertebrates, is characterized by supernumerary digits. In chickens, basic characteristics and rough dominant genes have been explored in past decades; however, the elaborate pattern of inheritance and the determinant gene remain obscure. In this study, different types of polydactylism were classified by the numbers and the shapes of toes, including the newly defined subtypes of B' and G, for the Beijing fatty chicken, a native breed of chicken from China. Through experiments on hybridization, we demonstrated a complete dominant inheritance of polydactyly instead of an incomplete penetrance or genetic modification of the previous conjecture. In particular, by using the F2 population of the five-digit purebred line of Beijing fatty chicken backcrossed to Shiqiza chicken and by using restriction-site associated DNA based markers, we performed a genome-wide association study on the trait of polydactyly. Furthermore, whole genome resequencing strategy was applied to sweep SNPs across the whole genome. An outlier-based Fst approach was employed to search for signatures of selection, and results indicated that the determinant mutation was found in the region ranging from 8.3 Mb to 8.7 Mb, where the polydactyly candidate gene LMBR1 was located. The G/T mutation of rs80659072 was identified to be highly associated with polydactyly in our resequencing and was validated in random samples from an expanded population. Thus, we confirmed that LMBR1 was the causative gene of polydactyly in the Beijing fatty chicken by using GWAS with restriction-site associated DNA based markers and resequencing.
Topics: Animals; Chickens; Chromosome Mapping; Genes, Dominant; Mutation; Polydactyly; Polymorphism, Single Nucleotide
PubMed: 28489934
DOI: 10.1371/journal.pone.0176113 -
Journal of Perinatal Medicine Mar 2016Mid trimester fetal anatomy scan is a fundamental part of routine antenatal care. Some U/S soft markers or controversial U/S signs are seen during the scan and create... (Review)
Review
Mid trimester fetal anatomy scan is a fundamental part of routine antenatal care. Some U/S soft markers or controversial U/S signs are seen during the scan and create some confusion regarding their relation to fetal chromosomal abnormalities. Example of these signs: echogenic focus in the heart, echogenic bowel, renal pyelectasis, ventriculomegaly, polydactely, club foot, choroid plexus cyst, single umbilical artery. We are presenting an evidence based approach from the literature for management of these controversial U/S signs.
Topics: Brain Diseases; Cardiomegaly; Choroid Plexus; Clubfoot; Congenital Abnormalities; Cysts; Echocardiography; Echogenic Bowel; Evidence-Based Medicine; Female; Humans; Infant, Newborn; Male; Polydactyly; Pregnancy; Pregnancy Trimester, Second; Pyelectasis; Single Umbilical Artery; Ultrasonography, Prenatal
PubMed: 26506099
DOI: 10.1515/jpm-2015-0223 -
World Journal of Plastic Surgery 2023Polydactyly is a congenital anomaly with a wide range of manifestations that occurs in many forms, ranging from varying degrees of mere splitting to completely...
Polydactyly is a congenital anomaly with a wide range of manifestations that occurs in many forms, ranging from varying degrees of mere splitting to completely duplicated thumb. When duplication occurs alone, it is usually unilateral and sporadic. In this case report, I report left hand polydactyly with 2 more fingers on 5 finger in a 6 month old male. He subsequently underwent surgical correction, and the over number thumb was removed with associated meticulous skeletal and soft tissue reconstruction. Polydactyly is the most common congenital digital anomaly of the hand and foot. It can occur in isolation or as part of a syndrome. Surgery is necessary to create a single, functioning thumb indicated to improve cosmetics. Skin, nail, bone, ligament, and musculoskeletal elements must be combined to reconstruct an optimal digit. Treatment options of polydactyly depend on the type and the underlying features. In the literature, different surgical treatments for lateral and medial polydactyly are described.
PubMed: 37220579
DOI: 10.52547/wjps.12.1.95