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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 -
Journal of Medical Genetics Apr 2023Ellis-Van Creveld (EVC) syndrome is one of the entities belonging to the skeletal ciliopathies short rib-polydactyly subgroup. Major signs are ectodermal dysplasia,...
BACKGROUND
Ellis-Van Creveld (EVC) syndrome is one of the entities belonging to the skeletal ciliopathies short rib-polydactyly subgroup. Major signs are ectodermal dysplasia, chondrodysplasia, polydactyly and congenital cardiopathy, with a high degree of variability in phenotypes ranging from lethal to mild clinical presentations. The and genes are the major genes causative of EVC syndrome. However, an increased number of genes involved in the ciliopathy complex have been identified in EVC syndrome, leading to a better understanding of its physiopathology, namely, , , , , and . They all code for proteins located in the primary cilia, playing a key role in signal transduction of the Hedgehog pathways.
METHODS
The aim of this study was the analysis of 50 clinically identified EVC cases from 45 families to further define the phenotype and molecular bases of EVC.
RESULTS
Our detection rate in the cohort of 45 families was of 91.11%, with variants identified in (77.8%), (6.7%), (2.2%), (2.2%) or (2.2%). No distinctive feature was remarkable of a specific genotype-phenotype correlation. Interestingly, we identified a high proportion of heterozygous deletions in of variable sizes (26.92%), mostly inherited from the mother, and probably resulting from recombinations involving Alu sequences.
CONCLUSION
We confirmed that and are the major genes involved in the EVC phenotype and highlighted the high prevalence of previously unreported CNVs (Copy Number Variation).
Topics: Humans; Hedgehog Proteins; Ellis-Van Creveld Syndrome; DNA Copy Number Variations; Phenotype; Polydactyly
PubMed: 35927022
DOI: 10.1136/jmg-2022-108435 -
Indian Journal of Nephrology 2022Bardet-Biedl syndrome (BBS) is a rare disorder with a frequency of 1:1,60,000. The disease is inherited in an autosomal recessive manner. Less than 15 cases have been...
Bardet-Biedl syndrome (BBS) is a rare disorder with a frequency of 1:1,60,000. The disease is inherited in an autosomal recessive manner. Less than 15 cases have been reported from India. We present a case of Bardet-Biedl syndrome presenting to the medical emergency with acute breathlessness because of de-compensated renal failure and salient features such as marked polydactyly, central obesity, retinitis pigmentosa, end-stage renal diseases, and mental retardation. Genetic study showed that the patient had BBS genetic variant 9 (MIM#615896), VUS variant. The patient was primarily treated for end-stage chronic renal failure with hemodialysis. We are reporting this case for its rarity and the presence of a novel genetic variant of an unidentified significance as per genome mapping. BBS is often not diagnosed at all or diagnosed late until end-stage renal failure sets in. Timely diagnosis might not help treat the condition but surely improve the quality of life for the patient.
PubMed: 36704599
DOI: 10.4103/ijn.ijn_320_21 -
Journal of Plastic, Reconstructive &... Nov 2021Despite lower extremity polydactyly (LEP) representing the most common congenital foot anomaly with functional and psychosocial implications, the literature is devoid of... (Review)
Review
BACKGROUND
Despite lower extremity polydactyly (LEP) representing the most common congenital foot anomaly with functional and psychosocial implications, the literature is devoid of comprehensive, synthesizing reviews. The purpose of the current review is to identify an evidence-based approach to guide clinical management and shed light on reported functional and esthetic outcomes for postaxial polydactyly.
METHODS
A scoping systematic review of primary clinical studies was performed. Baseline patient characteristics, diagnostic, and surgical approaches were recorded. Main outcomes included immediate postoperative pain, infections, callouses, scar cosmesis, residual deformities, and difficulty with shoe-wear or mobility. A qualitative synthesis of outcomes was performed, and a therapeutic algorithm was developed.
RESULTS
Nine primary studies were identified representing 375 cases of LEP; mean age was 28.8 months (range: 20-40.6 months), and mean follow-up: 42.7 months (range: 1 month-41 years). Ray dominance and the presence of syndactyly were identified as the most important factors for surgical planning; age at surgery was insignificant. A lateral incision approach was used in 78% of cases. Postoperative callouses occurred in 22.1% of cases, infections in 2.5%, and intermittent pain in 11.9%. Significant issues with shoe-wear or mobilization and esthetic residual deformities were reported for 0.78% and 41.2% of cases, respectively. The incidence of residual valgus was 10.6%.
CONCLUSION
LEP is most commonly managed with excision of the non-dominant ray and carries excellent long-term functional outcomes, as presented herein. Numerous techniques are discussed to minimize the risk of esthetic sequalae, although the presence of residual valgus remains a concern. A therapeutic algorithm is proposed for the optimal management of LEP.
Topics: Esthetics; Fingers; Forecasting; Humans; Polydactyly; Toes
PubMed: 33992559
DOI: 10.1016/j.bjps.2021.03.094 -
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 -
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 -
American Journal of Medical Genetics.... Sep 2023Two children are presented who have a distinct syndrome of multiple buccolingual frenula, a stiff and short fifth finger with small nails, a hypothalamic hamartoma, mild...
Two children are presented who have a distinct syndrome of multiple buccolingual frenula, a stiff and short fifth finger with small nails, a hypothalamic hamartoma, mild to moderate neurological impairment, and mild endocrinological symptoms. No variant assessed to be pathogenic or likely pathogenic was detected in the GLI3 gene in either child. This syndrome appears to be distinct from the inherited Pallister-Hall syndrome associated with GLI3 variants, which is characterized by hypothalamic hamartoma, mesoaxial polydactyly, and other anomalies. In the individuals described here, manifestations outside of the central nervous system were milder and the mesoaxial polydactyly, which is common in individuals with Pallister-Hall syndrome, was absent. Instead, these children had multiple buccolingual frenula together with the unusual appearance of the fifth digit. It remains unclear whether these two individuals represent a separate nosologic entity or if they represent a milder manifestation of one of the more severe syndromes associated with a hypothalamic hamartoma.
Topics: Child; Humans; Pallister-Hall Syndrome; Hamartoma; Hypothalamic Diseases; Polydactyly
PubMed: 37435845
DOI: 10.1002/ajmg.a.63306 -
Clinical Dysmorphology Jul 2022Laurin-Sandrow syndrome also known as tetramelic mirror-image polydactyly is a rare congenital disorder characterized classically by polysyndactyly of the hands, mirror... (Review)
Review
INTRODUCTION
Laurin-Sandrow syndrome also known as tetramelic mirror-image polydactyly is a rare congenital disorder characterized classically by polysyndactyly of the hands, mirror feet and nose anomalies (hypoplasia of the nasal alae and short columella) often associated with ulnar and/or fibular duplication. As a pathologic entity, it is heterogeneous, the patients displaying a variety of symptoms. This review aims to analyze the different aspects of the condition, such as clinical findings and methods of treatment to summarize the principal features of Laurin-Sandrow syndrome.
MATERIALS AND METHODS
The review is based on searches on PubMed, Web of Science and Researchgate of the following terms: "Laurin-Sandrow syndrome", "mirror hands", "mirror feet", "tetramelic mirror-image polydactyly", "fibular dimelia" and "ulnar dimelia". Clinical cases, reviews and original articles were included.
RESULTS
As a consequence of our findings, we suggest a modification of the Al-Qattan classification system for Mirror Hand-Multiple Hand Spectrum.
CONCLUSION
Even though it has an extremely low incidence, a thorough understanding of the syndrome enables the surgeon to choose the appropriate treatment with the ultimate goal to improve the patient's life quality.
Topics: Abnormalities, Multiple; Ectromelia; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Nose; Polydactyly
PubMed: 35256564
DOI: 10.1097/MCD.0000000000000420