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Journal of Feline Medicine and Surgery Dec 2020Polydactyly has been described in two breeds of domestic cats (Maine Coon and Pixie Bob) and in some outbred domestic cats (eg, Hemingway cats). In most cases, feline...
OBJECTIVES
Polydactyly has been described in two breeds of domestic cats (Maine Coon and Pixie Bob) and in some outbred domestic cats (eg, Hemingway cats). In most cases, feline polydactyly is a non-syndromic preaxial polydactyly. Three variants located in a regulatory sequence involved in limb development, named ZRS (zone of polarising activity regulatory sequence), have been identified to be responsible for feline polydactyly. These variants have been found in outbred domestic cats in the UK ( and variants) and in Hemingway cats in the USA ( variant). The aim of this study was to characterise the genetic features of polydactyly in Maine Coon cats.
METHODS
Genotyping assay was used to identify the variant(s) segregating in a cohort of 75 polydactyl and non-polydactyl Maine Coon cats from different breeding lines from Europe, Canada and the USA. The authors performed a segregation analysis to identify the inheritance pattern of polydactyly in this cohort and analysed the population structure.
RESULTS
The allele was identified in a subset of polydactyl cats. Sequencing of two regulatory sequences involved in limb development did not reveal any other variant in polydactyl cats lacking the allele. Additionally, genotype-phenotype and segregation analyses revealed the peculiar inheritance pattern of polydactyly in Maine Coon cats. The population structure analysis demonstrated a genetic distinction between and -free polydactyl cats.
CONCLUSIONS AND RELEVANCE
Polydactyly in Maine Coon cats is inherited as an autosomal dominant trait with incomplete penetrance and variable expressivity, and this trait is characterised by genetic heterogeneity in the Maine Coon breed. Maine Coon breeders should be aware of this situation and adapt their breeding practices accordingly.
Topics: Animals; Canada; Cats; Europe; Female; Genetic Heterogeneity; Male; Polydactyly; United States
PubMed: 32067556
DOI: 10.1177/1098612X20905061 -
Genes May 2023Bardet-Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous autosomal recessive multi-systemic disorder with 22 known genes. The primary clinical and...
Bardet-Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous autosomal recessive multi-systemic disorder with 22 known genes. The primary clinical and diagnostic features include six different hallmarks, such as rod-cone dystrophy, learning difficulties, renal abnormalities, male hypogonadism, post-axial polydactyly, and obesity. Here, we report nine consanguineous families and a non-consanguineous family with several affected individuals presenting typical clinical features of BBS. In the present study, 10 BBS Pakistani families were subjected to whole exome sequencing (WES), which revealed novel/recurrent gene variants, including a homozygous nonsense mutation (c.94C>T; p.Gln32Ter) in the (NM_006860.5) gene in family A, a homozygous nonsense mutation (c.160A>T; p.Lys54Ter) in the (NM_001195306.1) gene in family B, a homozygous nonsense variant (c.720C>A; p.Cys240Ter) in the (NM_015910.7) in family C, a homozygous nonsense variant (c.505A>T; p.Lys169Ter) in the (NM_020347.4) in family D, pathogenic homozygous 1 bp deletion (c.775delA; p.Thr259Leufs*21) in the / (NM_170784.3) gene in family E, a pathogenic homozygous missense variant (c.1339G>A; p.Ala447Thr) in (NM_024649.4) in families F and G, a pathogenic homozygous donor splice site variant (c.951+1G>A; p?) in (NM_024649.4) in family H, a pathogenic bi-allelic nonsense variant in (NM_170784.3) (c.119C>G; p.Ser40*) in family I, and homozygous pathogenic frameshift variants (c.196delA; p.Arg66Glufs*12) in (NM_152384.3) in family J. Our findings extend the mutation and phenotypic spectrum of four different types of ciliopathies causing BBS and also support the importance of these genes in the development of multi-systemic human genetic disorders.
Topics: Humans; Male; Bardet-Biedl Syndrome; Codon, Nonsense; Mutation; Polydactyly; Ciliopathies; Microtubule-Associated Proteins; Cytoskeletal Proteins; Phosphate-Binding Proteins
PubMed: 37239474
DOI: 10.3390/genes14051113 -
Genes Aug 2021Bardet-Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely... (Review)
Review
Bardet-Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely polymorphic. The main clinical features are retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, hypogonadism and genitourinary abnormalities, and kidney disease. It is caused by various types of mutations, mainly in genes encoding BBSome proteins, chaperonins, and IFT complex. Variable expressivity and pleiotropy are correlated with the existence of multiple genes and variants modifiers. This review is focused on the phenomena of heterogeneity (locus, allelic, mutational, and clinical) in Bardet-Biedl Syndrome, its mechanisms, and importance in early diagnosis and proper management.
Topics: Bardet-Biedl Syndrome; Fingers; Genetic Association Studies; Genetic Pleiotropy; Humans; Microtubule-Associated Proteins; Mutation; Polydactyly; Protein Interaction Maps; Toes
PubMed: 34573333
DOI: 10.3390/genes12091353 -
Clinical Medicine Insights. Pediatrics 2015Neonatal hydrometrocolpos (HMC) is a rare Mullerian duct anomaly with an incidence of 0.006%. It occurs due to blockage of the vagina with accumulation of mucus...
Neonatal hydrometrocolpos (HMC) is a rare Mullerian duct anomaly with an incidence of 0.006%. It occurs due to blockage of the vagina with accumulation of mucus secretions proximal to the obstacle. These secretions are secondary to intrauterine and postnatal stimulation of uterine and cervical glands by maternal estrogens. A triad of congenital HMC, polydactyly, and cardiac anomalies are the cardinal features of McKusick-Kaufman syndrome, which is also known as hydrometrocolpos-polydactyly syndrome. Bardet-Biedl syndrome is a well-known combination of hypogonadism, obesity, postaxial polydactyly, renal dysplasia, retinal degeneration, and mental impairment. In this case report, we describe a neonate with HMC, polydactyly, and hydronephrosis.
PubMed: 25635170
DOI: 10.4137/CMPed.S20787 -
Annals of Translational Medicine Aug 2021Few studies have investigated families in which multiple individuals over three or more generations are affected by radial polydactyly and syndactyly. This report...
BACKGROUND
Few studies have investigated families in which multiple individuals over three or more generations are affected by radial polydactyly and syndactyly. This report describes an extremely rare family in which nine individuals across six generations were affected by complex radial polydactyly.
METHODS
We investigated a six-generation pedigree with radial polydactyly including triplication, triphalangism, hypoplasia, and symphalangism. There was a total of 34 individuals (including their spouses) in the family and 11 individuals had polydactyly. The average age of the patients ranged from 7 months to 96 years. The characteristic feature of the malformation in these patients was described. Two patients underwent surgical resection for radial supernumerary thumbs. The Bilhout-Cloquet technique and On-top-plasty technique were used to reconstruct the nail and the joints.
RESULTS
The patients in this family presented with thumb duplication and triphalangism in both hands, including a variety of deformities, such as triplication, triphalangism, hypoplasia, and symphalangism. Syndactyly and ulnar polydactyly were also frequently observed. Two patients who underwent surgical treatment showed good hand and thumb function at the 8- and 2-year post-operative follow-up, respectively.
CONCLUSIONS
The present study reported various mixed phenotypes including triplication, triphalangism, hypoplasia, and symphalangism within the same family which may represent a rare type of polydactyly. Surgical resection of extra digits to achieve mobility of the thumb is the main treatment option for radial polydactyly. Given the ulnar thumb is better developed, the radial thumb is typically resected in patients with radial polydactyly. These reconstructive principles are fit for this Chinese family as well.
PubMed: 34532433
DOI: 10.21037/atm-21-2773 -
Taiwanese Journal of Obstetrics &... Mar 2007Meckel syndrome (MKS) is a lethal, autosomal recessive disorder characterized by occipital encephalocele, bilateral renal cystic dysplasia, hepatic ductal proliferation,... (Review)
Review
Meckel syndrome (MKS) is a lethal, autosomal recessive disorder characterized by occipital encephalocele, bilateral renal cystic dysplasia, hepatic ductal proliferation, fibrosis and cysts, and polydactyly. Genetic heterogeneity of MKS has been established by three reported MKS loci, i.e., MKS1 on 17q23, MKS2 on 11q13, and MKS3 on 8q21.13-q22.1. MKS1 encodes a component of flagellar apparatus basal body proteome, which is associated with ciliary function. MKS3 encodes a seven-transmembrane receptor protein, meckelin. The identification of the MKS3 gene as well as the MKS1 gene enables molecular genetic testing for at-risk families, and allows accurate genetic counseling, carrier testing, and prenatal diagnosis. Pregnancies with MKS fetuses may be associated with an elevated maternal serum alpha-fetoprotein level and an abnormal screening result in the second-trimester maternal serum screening test. The classic MKS triad of occipital encephalocele, postaxial polydactyly, and bilateral enlarged multicystic kidneys can be diagnosed before the 14th gestational weeks by ultrasonography. However, later in pregnancy, severe oligohydramnios may make the diagnosis of polydactyly and encephalocele difficult. Differential diagnosis for MKS includes autosomal recessive polycystic kidney disease, trisomy 13, Smith-Lemli-Opitz syndrome, hydrolethalus syndrome, Senior-Loken syndrome, Joubert syndrome, Bardet-Biedl syndrome, and oral-facial-digital syndrome type 1. This article provides an overview of genetics, perinatal findings, and differential diagnosis of MKS. The ciliopathy underlies the pathogenesis of MKS. Prenatal diagnosis of bilateral enlarged multicystic kidneys should alert MKS and prompt a thorough investigation of central nervous system malformations and polydactyly.
Topics: Abnormalities, Multiple; Cerebellum; Diagnosis, Differential; Encephalocele; Female; Fetal Diseases; Fingers; Genetic Testing; Humans; Kidney Diseases, Cystic; Liver Diseases; Polydactyly; Pregnancy; Prenatal Diagnosis; Syndrome; Toes
PubMed: 17389183
DOI: 10.1016/S1028-4559(08)60100-X -
International Journal of Molecular... Mar 2021We are conducting a clinical study of the use of allogeneic polydactyly-derived chondrocyte sheets (PD sheets) for the repair of articular cartilage damage caused by...
We are conducting a clinical study of the use of allogeneic polydactyly-derived chondrocyte sheets (PD sheets) for the repair of articular cartilage damage caused by osteoarthritis. However, the transplantation of PD sheets requires highly invasive surgery. To establish a less invasive treatment, we are currently developing injectable fragments of PD sheets (PD sheets-mini). Polydactyly-derived chondrocytes were seeded in RepCell™ or conventional temperature-responsive inserts and cultured. Cell counts and viability, histology, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), and flow cytometry were used to characterize PD sheets-mini and PD sheets collected from each culture. To examine the effects of injection on cell viability, PD sheets-mini were tested in four experimental conditions: non-injection control, 18 gauge (G) needle, 23G needle, and syringe only. PD sheets-mini produced similar amounts of humoral factors as PD sheets. No histological differences were observed between PD sheets and PD sheets-mini. Except for , expression of cartilage-related genes did not differ between the two types of PD sheet. No significant differences were observed between injection conditions. PD sheets-mini have characteristics that resemble PD sheets. The cell viability of PD sheets-mini was not significantly affected by needle gauge size. Intra-articular injection may be a feasible, less invasive method to transplant PD sheets-mini.
Topics: Animals; Biomarkers; Cartilage, Articular; Cell Count; Cell Survival; Chondrocytes; Gene Expression; Humans; Immunohistochemistry; Immunophenotyping; Osteoarthritis; Polydactyly; Regeneration; Tissue Scaffolds
PubMed: 33801144
DOI: 10.3390/ijms22063198 -
International Journal of Molecular... Sep 2021The Hedgehog (HH) signalling pathway is one of the major pathways controlling cell differentiation and proliferation during human development. This pathway is complex,... (Review)
Review
The Hedgehog (HH) signalling pathway is one of the major pathways controlling cell differentiation and proliferation during human development. This pathway is complex, with HH function influenced by inhibitors, promotors, interactions with other signalling pathways, and non-genetic and cellular factors. Many aspects of this pathway are not yet clarified. The main features of Sonic Hedgehog (SHH) signalling are discussed in relation to its function in human development. The possible role of SHH will be considered using examples of holoprosencephaly and short-rib polydactyly (SRP) syndromes. In these syndromes, there is wide variability in phenotype even with the same genetic mutation, so that other factors must influence the outcome. mutations were the first identified genetic causes of holoprosencephaly, but many other genes and environmental factors can cause malformations in the holoprosencephaly spectrum. Many patients with SRP have genetic defects affecting primary cilia, structures found on most mammalian cells which are thought to be necessary for canonical HH signal transduction. Although SHH signalling is affected in both these genetic conditions, there is little overlap in phenotype. Possible explanations will be canvassed, using data from published human and animal studies. Implications for the understanding of SHH signalling in humans will be discussed.
Topics: Animals; Cilia; Ciliopathies; Hedgehog Proteins; Holoprosencephaly; Humans; Short Rib-Polydactyly Syndrome; Signal Transduction
PubMed: 34576017
DOI: 10.3390/ijms22189854 -
Joint Diseases and Related Surgery 2022This study aims to compare the usefulness of two systems in classifying thumb duplication cases and give some examples of the cases we believe that are unclassifiable.
OBJECTIVES
This study aims to compare the usefulness of two systems in classifying thumb duplication cases and give some examples of the cases we believe that are unclassifiable.
PATIENTS AND METHODS
Between January 2011 and January 2018, a total of 50 patients (29 males, 21 females; median age: 46.4±68.3 months; range, 1 to 318 months) with thumb duplications as assessed according to the Wassel and Rotterdam classification systems were included.
RESULTS
Duplication was present in the right hand in 28, in the left hand in 21, and in both hands in one patient. According to the Wassel classification system, 45 patients could be allocated in any of the types; however, five patients could not be classified. According to the Rotterdam classification, 47 cases fell into one of the classifications; however, three cases could not be classified.
CONCLUSION
Despite efforts to find the best classification system for thumb duplications, the proposed systems may not fully cover the presented radial polydactyly cases, and additions to the system are required.
Topics: Child; Child, Preschool; Female; Humans; Male; Polydactyly; Thumb
PubMed: 35361090
DOI: 10.52312/jdrs.2022.482 -
BMC Pregnancy and Childbirth Mar 2024To describe the prevalence and epidemiology of congenital polydactyly and syndactyly in Hunan Province, China, 2016-2020.
OBJECTIVE
To describe the prevalence and epidemiology of congenital polydactyly and syndactyly in Hunan Province, China, 2016-2020.
METHODS
Data were obtained from the Birth Defects Surveillance System in Hunan Province, China, 2016-2020. Prevalence of birth defects (polydactyly or syndactyly) is the number of cases per 1000 births (unit: ‰). Prevalence and 95% confidence intervals (CI) were calculated by the log-binomial method. Chi-square trend tests (χ) were used to determine trends in prevalence by year. Crude odds ratios (ORs) were calculated to examine the association of each demographic characteristic with polydactyly and syndactyly.
RESULTS
Our study included 847,755 births, and 14,459 birth defects were identified, including 1,888 polydactyly and 626 syndactyly cases, accounting for 13.06% and 4.33% of birth defects, respectively. The prevalences of total birth defects, polydactyly, and syndactyly were 17.06‰ (95%CI: 16.78-17.33), 2.23‰ (95%CI: 2.13-2.33), and 0.74‰ (95%CI: 0.68-0.80), respectively. Most polydactyly (96.77%) and syndactyly (95.69%) were diagnosed postnatally (within 7 days). From 2016 to 2020, the prevalences of polydactyly were 1.94‰, 2.07‰, 2.20‰, 2.54‰, and 2.48‰, respectively, showing an upward trend (χ = 19.48, P < 0.01); The prevalences of syndactyly were 0.62‰, 0.66‰, 0.77‰, 0.81‰, and 0.89‰, respectively, showing an upward trend (χ = 10.81, P = 0.03). Hand polydactyly (2.26‰ vs. 1.33‰, OR = 1.69, 95%CI: 1.52-1.87) and hand syndactyly (0.43‰ vs. 0.28‰, OR = 1.42, 95%CI: 1.14-1.76) were more common in males than females. Polydactyly (2.67‰ vs. 1.93‰, OR = 1.38, 95%CI: 1.26-1.51) and syndactyly (0.91‰ vs. 0.62‰, OR = 1.47, 95%CI: 1.26-1.72) were more common in urban areas than in rural areas. Compared to maternal age 25-29, hand polydactyly was more common in maternal age < 20 (2.48‰ vs. 1.74‰, OR = 1.43, 95%CI: 1.01-2.02) or ≥ 35 (2.25‰ vs. 1.74‰, OR = 1.30, 95%CI: 1.12-1.50).
CONCLUSION
In summary, we have described the prevalence and epidemiology of polydactyly and syndactyly from hospital-based surveillance in Hunan Province, China, 2016-2020. Our findings make some original contributions to the field, which may be valuable for future research.
Topics: Male; Female; Humans; Adult; Polydactyly; Syndactyly; Maternal Age; China; Prevalence; Congenital Abnormalities
PubMed: 38521899
DOI: 10.1186/s12884-024-06417-y