A large Turkish kindred with syndactyly type II (synpolydactyly). 1. Field investigation, clinical and pedigree data.

Sayli, B S; Akarsu, Ayşegül; Sayli, U; Akhan, O; Ceylaner, Serdar; Sarfarazi, Mansoor

doi:10.1136/jmg.32.6.421

Cited by 35 publications

(30 citation statements)

References 9 publications

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“…The slight exception seen for foot involvement in individuals with 8-alanine expansions is probably due to their small number. The figures for individuals with 9-alanine expansions are closely comparable to those of Sayli et al (6). The individuals with 10-and 14-alanine expansions were all from pedigrees 3 and Q, respectively.…”

Section: Pedigreessupporting

confidence: 77%

“…SPD typically consists of 3͞4 finger and 4͞5 toe syndactyly, with a duplicated digit in the syndactylous web (3). Incomplete penetrance and variable expressivity both between and within affected families are common (4)(5)(6). From one to four limbs can be involved, and the severity of involvement ranges from partial skin syndactyly to complete reduplication of a digit, extending as far proximally as the metacarpals͞tarsals.…”

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confidence: 99%

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Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract

Goodman

Mundlos

Muragaki

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

200

184

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Synpolydactyly (SPD) is a dominantly inherited congenital limb malformation. Typical cases have 3͞4 finger and 4͞5 toe syndactyly, with a duplicated digit in the syndactylous web, but incomplete penetrance and variable expressivity are common. The condition has recently been shown to be caused by expansions of an imperfect trinucleotide repeat sequence encoding a 15-residue polyalanine tract in HOXD13. We have studied 16 new and 4 previously published SPD families, with between 7 and 14 extra residues in the tract, to analyze the molecular basis for the observed variation in phenotype. Although there is no evidence of change in expansion size within families, even over six generations, there is a highly significant increase in the penetrance and severity of phenotype with increasing expansion size, affecting both hands (P ‫؍‬ 0.012) and feet (P < 0.00005). Affected individuals from a family with a 14-alanine expansion, the largest so far reported, all have a strikingly similar and unusually severe limb phenotype, involving the first digits and distal carpals. Affected males from this family also have hypospadias, not previously described in SPD, but consistent with HOXD13 expression in the developing genital tubercle. The remarkable correlation between phenotype and expansion size suggests that expansion of the tract leads to a specific gain of function in the mutant HOXD13 protein, and has interesting implications for the role of polyalanine tracts in the control of transcription.Dominantly inherited disorders frequently display incomplete penetrance (a normal phenotype in some mutation carriers) and variable expressivity (different degrees of phenotypic severity in affected individuals), the molecular basis for which is generally not understood. One such disorder is the rare dominantly inherited congenital limb malformation, synpolydactyly (SPD; OMIM No. 186000). Mutations in the first exon of HOXD13 have recently been found in three American SPD families (1), expanding a 15-residue polyalanine tract encoded by an imperfect trinucleotide repeat sequence by 7, 8, and 10 additional residues, respectively. Similar 9-residue expansions subsequently have been reported in two Turkish SPD families (2). SPD typically consists of 3͞4 finger and 4͞5 toe syndactyly, with a duplicated digit in the syndactylous web (3). Incomplete penetrance and variable expressivity both between and within affected families are common (4-6). From one to four limbs can be involved, and the severity of involvement ranges from partial skin syndactyly to complete reduplication of a digit, extending as far proximally as the metacarpals͞tarsals. Associated distal limb abnormalities include fifth-finger clinodactyly, camptodactyly, or brachydactyly; variable syndactyly of the second to fifth toes; and middle phalanx hypoplasia͞ aplasia.To investigate the molecular basis for this incomplete penetrance and variable expressivity, we analyzed the genotype and phenotype of 16 new SPD pedigrees, including one with an expansion that almost doub...

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Section: Pedigreessupporting

confidence: 77%

mentioning

confidence: 99%

Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract

Goodman

Mundlos

Muragaki

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

200

184

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“…These two features were seen in the two affected girls of the second family. Sayli et al 10 showed that some family members may show polydactyly of the little finger and this was seen in one child of the first family. Several authors 5,11,12 showed that clinodactyly of the little finger may be a concurrent or isolated feature, indicating that the responsible gene may be expressed as an isolated clinodactyly and this was seen in the parents of the second family.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9][10][11][12] It is characterized by bilateral synpolydactyly of the third web spaces of the hands and bilateral synpolydactyly of the fourth web spaces of the feet. It is inherited as autosomal dominant and the mutation has been localized to 2q31 (HOXD13).…”

Section: Introductionmentioning

confidence: 99%

Type II familial synpolydactyly: report on two families with an emphasis on variations of expression

Al‐Qattan

2010

Eur J Hum Genet

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Type II familial synpolydactyly is rare and is known to have variable expression. However, no previous papers have attempted to review these variations. The aim of this paper was to review these variations and show several of these variable expressions in two families. The classic features of type II familial synpolydactyly are bilateral synpolydactyly of the third web spaces of the hands and bilateral synpolydactyly of the fourth web spaces of the feet. Several members of the two families reported in this paper showed the following variations: the third web spaces of the hands showing syndactyly without the polydactyly, normal feet, concurrent polydactyly of the little finger, concurrent clinodactyly of the little finger and the 'homozygous' phenotype. It was concluded that variable expressions of type II familial synpolydactyly are common and awareness of such variations is important to clinicians.

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“…The expression of SPD varies, and incomplete penetrance is estimated at 86% to 97% (Goodman et al, 1997;Sayli et al, 1995). SPD is classified into 3 categories, SPD1, SPD2, and SPD3, by SPD loci mapped to chromosome 2q31, 22q13.31, and 14q11.2-q12, respectively (Malik and Grzeschik, 2008;Temtamy and McKusick, 1978).…”

Section: Introductionmentioning

confidence: 99%

Eight-alanine duplication in homeobox D13 in a Chinese family with synpolydactyly

Qian

et al. 2012

Gene

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A large Turkish kindred with syndactyly type II (synpolydactyly). 1. Field investigation, clinical and pedigree data.

Cited by 35 publications

References 9 publications

Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract

Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract

Type II familial synpolydactyly: report on two families with an emphasis on variations of expression

Eight-alanine duplication in homeobox D13 in a Chinese family with synpolydactyly

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