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PloS One 2016Polydactyly is one of the most common hereditary congenital limb malformations in chickens and other vertebrates. The zone of polarizing activity regulatory sequence...
Polydactyly is one of the most common hereditary congenital limb malformations in chickens and other vertebrates. The zone of polarizing activity regulatory sequence (ZRS) is critical for the development of polydactyly. The causative mutation of polydactyly in the Silkie chicken has been mapped to the ZRS; however, the causative mutations of other chicken breeds are yet to be established. To understand whether the same mutation decides the polydactyly phenotype in other chicken breeds, we detected the single-nucleotide polymorphism in 26 different chicken breeds, specifically, 24 Chinese indigenous breeds and 2 European breeds. The mutation was found to have fully penetrated chickens with polydactyly in China, indicating that it is causative for polydactyly in Chinese indigenous chickens. In comparison, the mutation showed no association with polydactyly in Houdan chickens, which originate from France, Europe. Based on the different morphology of polydactyly in Chinese and European breeds, we assumed that the trait might be attributable to different genetic foundations. Therefore, we subsequently performed genome-wide association analysis (GWAS) to locate the region associated with polydactyly. As a result, a ~0.39 Mb genomic region on GGA2p was identified. The region contains six candidate genes, with the causative mutation found in Chinese indigenous breeds also being located in this region. Our results demonstrate that polydactyly in chickens from China and Europe is caused by two independent mutation events that are closely located in the chicken genome.
Topics: Animals; Chickens; China; DNA; Europe; Genetic Association Studies; Genetic Linkage; Genome-Wide Association Study; Polydactyly; Polymerase Chain Reaction; Polymorphism, Single Nucleotide
PubMed: 26859147
DOI: 10.1371/journal.pone.0149010 -
Journal of Medical Case Reports May 2023Caroli disease is multifocal segmental dilatation of the large intrahepatic bile ducts that connect to the main duct. It is considered a rare disease with an incidence...
INTRODUCTION
Caroli disease is multifocal segmental dilatation of the large intrahepatic bile ducts that connect to the main duct. It is considered a rare disease with an incidence rate of 1 in 1,000,000 births. There are two types of Caroli: the first type is the simple type, Caroli disease, which includes only cystic dilatation of the intrahepatic bile ducts. The second is called Caroli syndrome, which consists of Caroli disease and congenital hepatic fibrosis and might lead to portal hypertension leading to esophageal varices and splenomegaly. Atrial septal defect is one of the most common congenital heart diseases, occurring when the connection between the left and the right atriums fails to close. Polydactyly is one of the most common congenital malformations of the hands and feet. It manifests in excess fingers on the hands or toes.
CASE PRESENTATION
A 6-year-old Arab girl presented to the hospital with abdominal pain for the last month with abdominal enlargement. The patient was already diagnosed with Caroli disease and polydactyly (six fingers on each limb) when she was born. Investigations including complete blood count, blood smear, bone marrow biopsy, esophagoscopy, abdominal ultrasound, and computed tomography scan showed splenomegaly associated with hypersplenism, fourth-grade non-bleeding varices, intrahepatic cystic formations in the left and right lobes, and an atrial septal defect with a left-to-right shunt. The patient was scheduled for a splenectomy after she was vaccinated with the appropriate vaccines. After follow-up for a week in the hospital, complete blood count showed an improvement. A month after that, the patient had liver abscesses and biliary fistula that were treated appropriately and her symptoms resolved.
CONCLUSION
The association of liver diseases, polydactyly, and congenital heart diseases is extremely rare and was only documented few times in the literature. However, to our knowledge, atrial septal defect has never been part of this combination before. The family history also makes this case unique and strongly suggests genetic etiology.
Topics: Female; Humans; Child; Caroli Disease; Splenomegaly; Bile Ducts, Intrahepatic; Polydactyly; Heart Septal Defects, Atrial
PubMed: 37217974
DOI: 10.1186/s13256-023-03919-9 -
The Journal of Neuroscience : the... Mar 2023Despite the tight coupling between sensory and motor processing for fine manipulation in humans, it is not yet totally clear which specific properties of the fingers are...
Despite the tight coupling between sensory and motor processing for fine manipulation in humans, it is not yet totally clear which specific properties of the fingers are mapped in the precentral and postcentral gyrus. We used fMRI to compare the morphology, connectivity, and encoding of the motor and tactile finger representations (FRs) in the precentral and postcentral gyrus of 25 5-fingered participants (8 females). Multivoxel pattern and structural and functional connectivity analyses demonstrated the existence of distinct motor and tactile FRs within both the precentral and postcentral gyrus, integrating finger-specific motor and tactile information. Using representational similarity analysis, we found that the motor and tactile FRs in the sensorimotor cortex were described by the perceived structure of the hand better than by the actual hand anatomy or other functional models (finger kinematics, muscles synergies). We then studied a polydactyly individual (i.e., with a congenital 6-fingered hand) showing superior manipulation abilities and divergent anatomic-functional hand properties. The perceived hand model was still the best model for tactile representations in the precentral and postcentral gyrus, while finger kinematics better described motor representations in the precentral gyrus. We suggest that, under normal conditions (i.e., in subjects with a standard hand anatomy), the sensorimotor representations of the 5 fingers in humans converge toward a model of perceived hand anatomy, deviating from the real hand structure, as the best synthesis between functional and structural features of the hand. Distinct motor and tactile finger representations exist in both the precentral and postcentral gyrus, supported by a finger-specific pattern of anatomic and functional connectivity across modalities. At the representational level, finger representations reflect the perceived structure of the hand, which might result from an adapting process harmonizing (i.e., uniformizing) the encoding of hand function and structure in the precentral and postcentral gyrus. The same analyses performed in an extremely rare polydactyly subject showed that the emergence of such representational geometry is also found in neuromechanical variants with different hand anatomy and function. However, the harmonization process across the precentral and postcentral gyrus might not be possible because of divergent functional-structural properties of the hand and associated superior manipulation abilities.
Topics: Female; Humans; Somatosensory Cortex; Fingers; Touch; Hand; Magnetic Resonance Imaging; Polydactyly; Brain Mapping
PubMed: 36717227
DOI: 10.1523/JNEUROSCI.1976-21.2022 -
Journal of Bone and Mineral Research :... Feb 2019Polydactyly is a common congenital anomaly of the hand and foot. Postaxial polydactyly (PAP) is characterized by one or more posterior or postaxial digits. In a... (Clinical Trial)
Clinical Trial
Polydactyly is a common congenital anomaly of the hand and foot. Postaxial polydactyly (PAP) is characterized by one or more posterior or postaxial digits. In a Pakistani family with autosomal recessive nonsyndromic postaxial polydactyly type A (PAPA), we performed genomewide genotyping, linkage analysis, and exome and Sanger sequencing. Exome sequencing revealed a homozygous nonsense variant (c.478C>T, p.[Arg160*]) in the FAM92A gene within the mapped region on 8q21.13-q24.12 that segregated with the PAPA phenotype. We found that FAM92A is expressed in the developing mouse limb and E11.5 limb bud including the progress zone and the apical ectodermal ridge, where it strongly localizes at the cilia level, suggesting an important role in limb patterning. The identified variant leads to a loss of the FAM92A/Chibby1 complex that is crucial for ciliogenesis and impairs the recruitment and the colocalization of FAM92A with Chibby1 at the base of the cilia. In addition, we show that Fam92a homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri. In conclusion, we present a new nonsyndromic PAPA ciliopathy due to a loss-of-function variant in FAM92A. © 2018 American Society for Bone and Mineral Research.
Topics: Animals; Carrier Proteins; Ciliopathies; Codon, Nonsense; Exome; Female; Fingers; Homozygote; Humans; Male; Mice; Mice, Knockout; Nuclear Proteins; Polydactyly; Proteins; Toes; Exome Sequencing
PubMed: 30395363
DOI: 10.1002/jbmr.3594 -
Taiwanese Journal of Obstetrics &... Sep 2008Fetuses with neural tube defects (NTDs) may suffer from associated syndromes and disorders. This article provides a comprehensive review of the syndromes and disorders... (Review)
Review
Fetuses with neural tube defects (NTDs) may suffer from associated syndromes and disorders. This article provides a comprehensive review of the syndromes and disorders associated with NTDs, including Pallister-Hall syndrome, Walker-Warburg syndrome and Fukuyama congenital muscular dystrophy, MURCS association, Roberts syndrome, cerebro-costo-mandibular syndrome, laterality sequences, hydrolethalus syndrome, Knobloch syndrome, oculoauriculovertebral spectrum (hemifacial microsomia), cervico-oculo-acoustic syndrome, Fanconi anemia, Miller-Dieker lissencephaly syndrome, Fraser syndrome, frontonasal dysplasia, Adams-Oliver syndrome, CHILD syndrome, dyssegmental dysplasia, and monozygotic twinning. NTDs associated with these syndromes and disorders are a rare but important cause of NTDs. The risk of NTDs in subsequent fetuses and the preventive effect of maternal folic acid intake in NTDs associated with syndromes and disorders may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes and disorders associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.
Topics: Abnormalities, Multiple; Congenital Abnormalities; Female; Humans; Infant, Newborn; Male; Maternal Welfare; Neural Tube Defects; Pallister-Hall Syndrome; Perinatal Care; Pregnancy; Prognosis; Risk Assessment; Severity of Illness Index; Survival Analysis; Syndrome; Taiwan
PubMed: 18935987
DOI: 10.1016/S1028-4559(08)60122-9 -
HGG Advances Oct 2023MYCN, a member of the MYC proto-oncogene family, regulates cell growth and proliferation. Somatic mutations of MYCN are identified in various tumors, and germline...
MYCN, a member of the MYC proto-oncogene family, regulates cell growth and proliferation. Somatic mutations of MYCN are identified in various tumors, and germline loss-of-function variants are responsible for Feingold syndrome, characterized by microcephaly. In contrast, one megalencephalic patient with a gain-of-function variant in MYCN, p.Thr58Met, has been reported, and additional patients and pathophysiological analysis are required to establish the disease entity. Herein, we report two unrelated megalencephalic patients with polydactyly harboring MYCN variants of p.Pro60Leu and Thr58Met, along with the analysis of gain-of-function and loss-of-function Mycn mouse models. Functional analyses for MYCN-Pro60Leu and MYCN-Thr58Met revealed decreased phosphorylation at Thr58, which reduced protein degradation mediated by FBXW7 ubiquitin ligase. The gain-of-function mouse model recapitulated the human phenotypes of megalencephaly and polydactyly, while brain analyses revealed excess proliferation of intermediate neural precursors during neurogenesis, which we determined to be the pathomechanism underlying megalencephaly. Interestingly, the kidney and female reproductive tract exhibited overt morphological anomalies, possibly as a result of excess proliferation during organogenesis. In conclusion, we confirm an MYCN gain-of-function-induced megalencephaly-polydactyly syndrome, which shows a mirror phenotype of Feingold syndrome, and reveal that MYCN plays a crucial proliferative role, not only in the context of tumorigenesis, but also organogenesis.
Topics: Mice; Animals; Humans; Female; Microcephaly; Gain of Function Mutation; N-Myc Proto-Oncogene Protein; Polydactyly; Phenotype; Megalencephaly; Eyelids; Intellectual Disability; Tracheoesophageal Fistula; Limb Deformities, Congenital
PubMed: 37710961
DOI: 10.1016/j.xhgg.2023.100238 -
Cureus Dec 2021Polydactyly is a common congenital malformation in which extra digits are present in at least one extremity. It has various presentations, and it can be an isolated...
Polydactyly is a common congenital malformation in which extra digits are present in at least one extremity. It has various presentations, and it can be an isolated anomaly or part of other diseases. Most isolated polydactyly cases are sporadic and unilateral, but there is an increased incidence in some populations. Polydactyly is multifactorial and can occur in different forms. Its main line of treatment is surgery to improve cosmesis and functioning. In this report, we present a rare case of bilateral complex hand polydactyly in a one-year-seven-months old girl of African descent. She is otherwise healthy with no family history of malformations. The pattern is not consistent with any syndromic disease. She subsequently underwent surgical resection of the extra digits.
PubMed: 35111490
DOI: 10.7759/cureus.20856 -
Clinical Dysmorphology Oct 2012Patients with a combination of holoprosencephaly and polydactyly, but with apparently normal chromosomes, may be clinically diagnosed with holoprosencephaly-polydactyly... (Review)
Review
Patients with a combination of holoprosencephaly and polydactyly, but with apparently normal chromosomes, may be clinically diagnosed with holoprosencephaly-polydactyly syndrome (HPS), also termed pseudotrisomy 13. However, the criteria for HPS have been controversial since the advent of the diagnostic term, and a clear understanding of the condition lacks definitive delineation. We review the historical and current perspectives on the condition and analyze findings in 40 patients with apparent HPS, including cases from the literature and two previously unreported patients. Overall, our analysis suggests previously unrecognized trends in patients diagnosed with HPS. Specifically, there appears to be a higher prevalence of visceral anomalies, most significantly cardiac and genitourinary, but also with increased gastrointestinal, pulmonary, adrenal, skeletal, and renal abnormalities, in patients with HPS. Although these visceral anomalies may not be essential for the identification of HPS, clinicians should be aware of the presence of such characteristics in these patients to optimize management and help establish etiologies.
Topics: Chromosomes, Human, Pair 13; Fetal Macrosomia; Fetus; Hand Deformities, Congenital; Holoprosencephaly; Humans; Infant; Infant, Newborn; Male; Polydactyly; Trisomy
PubMed: 22643382
DOI: 10.1097/MCD.0b013e3283551fd0 -
G3 (Bethesda, Md.) Apr 2014Polydactyly occurs in some chicken breeds, but the molecular mechanism remains incompletely understood. Combined genome-wide linkage analysis and association study...
Polydactyly occurs in some chicken breeds, but the molecular mechanism remains incompletely understood. Combined genome-wide linkage analysis and association study (GWAS) for chicken polydactyly helps identify loci or candidate genes for the trait and potentially provides further mechanistic understanding of this phenotype in chickens and perhaps other species. The linkage analysis and GWAS for polydactyly was conducted using an F2 population derived from Beijing-You chickens and commercial broilers. The results identified two QTLs through linkage analysis and seven single-nucleotide polymorphisms (SNPs) through GWAS, associated with the polydactyly trait. One QTL located at 35 cM on the GGA2 was significant at the 1% genome-wise level and another QTL at the 1% chromosome-wide significance level was detected at 39 cM on GGA19. A total of seven SNPs, four of 5% genome-wide significance (P < 2.98 × 10(-6)) and three of suggestive significance (5.96 × 10(-5)) were identified, including two SNPs (GGaluGA132178 and Gga_rs14135036) in the QTL on GGA2. Of the identified SNPs, the eight nearest genes were sonic hedgehog (SHH), limb region 1 homolog (mouse) (LMBR1), dipeptidyl-peptidase 6, transcript variant 3 (DPP6), thyroid-stimulating hormone, beta (TSHB), sal-like 4 (Drosophila) (SALL4), par-6 partitioning defective 6 homolog beta (Caenorhabditis elegans) (PARD6B), coenzyme Q5 (COQ5), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, etapolypeptide (YWHAH). The GWAS supports earlier reports of the importance of SHH and LMBR1 as regulating genes for polydactyly in chickens and other species, and identified others, most of which have not previously been associated with limb development. The genes and associated SNPs revealed here provide detailed information for further exploring the molecular and developmental mechanisms underlying polydactyly.
Topics: Animals; Chickens; Female; Genetic Association Studies; Genetic Linkage; Genome-Wide Association Study; Genotype; Male; Phenotype; Polydactyly; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Recombination, Genetic
PubMed: 24752238
DOI: 10.1534/g3.114.011338 -
Indian Journal of Dental Research :... 2013A case of a 10-year-old boy reported to us for delayed eruption of permanent teeth with classical features of orofacial digital syndrome (OFDS). The case of OFDS is...
A case of a 10-year-old boy reported to us for delayed eruption of permanent teeth with classical features of orofacial digital syndrome (OFDS). The case of OFDS is being reported and the various clinico-radiological features of both type I and type II are compared. Chromosomal karyotyping of the case has also been performed.
Topics: Child; Cleft Lip; Diagnosis, Differential; Humans; Karyotyping; Labial Frenum; Male; Orofaciodigital Syndromes; Polydactyly; Tongue
PubMed: 23852247
DOI: 10.4103/0970-9290.114920