Disease relevance of Polydactyly

• Using a bioinformatic screen for ciliary genes in combination with mutational analyses, we identified ARL6 as the gene underlying Bardet-Biedl syndrome type 3, a multisystemic disorder characterized by obesity, blindness, polydactyly, renal abnormalities and cognitive impairment [1].
• Bardet-Biedl syndrome (BBS) is a multisystemic disorder characterized by postaxial polydactyly, progressive retinal dystrophy, obesity, hypogonadism, renal dysfunction, and learning difficulty [2].
• We show here that treatment with Triparanol, a distal inhibitor of cholesterol biosynthesis, induced patterning defects of the autopod at high frequency, including pre-axial syndactyly and post-axial polydactyly, thus reproducing limb anomalies frequently observed in humans [3].
• Bardet-Biedl syndrome (BBS) is characterized by obesity, retinopathy, polydactyly, cognitive impairment, renal and cardiac anomalies as well as hypertension and diabetes [4].
• The linkage studies provide evidence that more than one locus is involved in bringing about the combination of CNS malformations, cystic kidneys, and polydactyly, maybe even in typical cases of MKS [5].

Psychiatry related information on Polydactyly

• Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic human disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism [6].
• Bardet-Biedl Syndrome (BBS) is an autosomal recessive disorder characterized by developmental abnormalities including mental retardation, obesity, retinitis pigmentosa, polydactyly, short stature, and hypogenitalism [7].

High impact information on Polydactyly

• Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder predominantly characterized by obesity, retinal dystrophy, polydactyly, learning difficulties, hypogenitalism and renal malformations, with secondary features that include diabetes mellitus, endocrinological dysfunction and behavioural abnormalities [8].
• Ellis-van Creveld syndrome (EvC, MIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth [9].
• The polydactyly of GCPS is commonly preaxial and that of PHS is typically central or postaxial [10].
• Point mutations in the long-range, limb-specific regulatory element of the SHH gene are responsible for the human limb abnormality called preaxial polydactyly (PPD) [11].
• We studied the involvement of GLI3 in additional phenotypes of digital abnormalities in one family (UR003) with preaxial polydactyly type-IV (PPD-IV), three families (UR014, UR015, and UR016) with dominant PAP-A/B (with PPD-A and -B in the same family), and one family with PHS [12].

Chemical compound and disease context of Polydactyly

• We describe a six-generation family in which a novel combination of brachydactyly and central polydactyly co-segregates with a missense mutation that substitutes leucine for isoleucine at position 47 of the HOXD13 homeodomain [13].
• Studies on induction of polydactyly in rats with cytosine arabinoside [14].
• Either duplication (preaxial polydactyly of hands and feet) or deficiency (absence of thumb) is a common effect of thalidomide; no other human teratogen identified to date has this effect on the developing limb [15].
• An infant born with preaxial polydactyly to a mother taking azathioprine throughout pregnancy is described [16].
• One newborn whose mother received coumarin during the first trimester had bilateral hand polydactylia [17].

Biological context of Polydactyly

• Truncation mutations of the GLI3 zinc finger transcription factor can cause Greig cephalopolysyndactyly syndrome (GCPS), Pallister-Hall syndrome (PHS), and postaxial polydactyly type A (PAP-A) [18].
• Postaxial polydactyly type A/B (PAP-A/B) is linked to chromosome 19p13.1-13.2 in a Chinese kindred [19].
• Frontonasal dysplasia, coronal craniosynostosis, pre- and postaxial polydactyly and split nails: a new autosomal dominant mutant with reduced penetrance and variable expression [20]?
• RESULTS: The triad of fetal occipital encephalocele, bilateral polycystic kidneys, and postaxial polydactyly was detected by transabdominal ultrasonography and confirmed by transvaginal scanning in 4 of the 9 pregnancies in the high-risk group [21].
• The reporter genes in the MDM were: barring (B), silver (S), creeper (Cp), rose comb (R), double uropygial gland (U), crest (Cr), dominant white (I), frizzle (F), duplex comb (D), multiple spurs (M), polydactyly (Po), blue egg (O), pea comb (P), naked neck (Na), extended black (E), white skin (W+), muffs and beard (Mb), and feathered shanks (Fsh) [22].

Anatomical context of Polydactyly

• Meckel syndrome (MKS) is a lethal syndrome with a central nervous system malformation, usually occipital meningoencephalocele, bilaterally large multicystic kidneys with fibrotic changes of the liver, and polydactyly in most cases [5].
• Bardet-Biedl syndrome (BBS) is a pleiotropic genetic disorder with the cardinal features of obesity, photoreceptor degeneration, polydactyly, hypogenitalism, renal abnormalities, and developmental delay [23].
• Major characteristics of the acrocallosal syndrome include severe mental retardation, agenesis or hypoplasia of the corpus callosum, and polydactyly of fingers and toes [24].
• Preaxial involvement of the upper extremities was most commonly seen at the SHFM3 locus mapped to chromosome 10q24 (OMIM 600095) and consisted of proximally placed thumbs and/or triphalangeal thumbs (TPT), preaxial polydactyly and/or absence of the first ray [25].
• The homozygous Polydactyly Nagoya (Pdn/Pdn) mice exhibit 1-3 extra digits both in the fore- and hindlimbs preaxially [26].

Gene context of Polydactyly

• Bardet-Biedl syndrome (BBS) is an uncommon multisystemic disorder characterized primarily by retinal dystrophy, obesity, polydactyly, and renal dysfunction [27].
• Mutations in a conserved non-coding region in intron 5 of the Lmbr1 locus, which is 1 Mb away from the sonic hedgehog (Shh) coding sequence, are responsible for mouse and human preaxial polydactyly with mirror-image digit duplications [28].
• We report here a series of nine patients diagnosed in infancy with MKKS because of the presence of vaginal atresia and postaxial polydactyly, who later developed obesity and retinal dystrophy, thus turning out to be instances of BBS [29].
• Mutations in the human GLI3 gene have been identified in Greig cepalopolysyndactyly, Pallister-Hall syndrome (PHS), and postaxial polydactyly type-A (PAP-A) [12].
• Mutations in the human homologue of csal1, termed Hsal1/SALL1, result in a condition known as Townes-Brocks syndrome (TBS), which is characterized by preaxial polydactyly [30].

References