Mutations affecting the BHLHA9 DNA-binding domain cause MSSD, mesoaxial synostotic syndactyly with phalangeal reduction, Malik-Percin type.

Mesoaxial synostotic syndactyly, Malik-Percin type (MSSD) (syndactyly type IX) is a rare autosomal-recessive nonsyndromic digit anomaly with only two affected families reported so far. We previously showed that the trait is genetically distinct from other syndactyly types, and through autozygosity mapping we had identified a locus on chromosome 17p13.3 for this unique limb malformation.

Synpolydactyly and HOXD13 polyalanine repeat: addition of 2 alanine residues is without clinical consequences.

Background: Type II syndactyly or synpolydactyly (SPD) is clinically very heterogeneous, and genetically three distinct SPD conditions are known and have been designated as SPD1, SPD2 and SPD3, respectively. SPD1 type is associated with expansion mutations in HOXD13, resulting in an addition of > or = 7 alanine residues to the polyalanine repeat. It has been suggested that expansions < or = 6 alanine residues go without medical attention, as no such expansion has ever been reported with the SPD1 phenotype.

Fifth finger camptodactyly maps to chromosome 3q11.2-q13.12 in a large German kindred.

Camptodactyly (MIM 114200) is a digit deformity characterised by permanent flexion contracture of fifth fingers at the proximal interphalangeal (PIP) joints. The sporadic cases are common but a familial occurrence is not much appreciated. In an attempt to identify the genetic basis of camptodactyly, we have analysed a large German family with camptodactyly segregating in an autosomal dominant fashion.

Evidence for clinical and genetic heterogeneity of syndactyly type I: the phenotype of second and third toe syndactyly maps to chromosome 3p21.31.

There is good evidence from the medical literature that type I syndactyly, the most common form of the nonsyndromic syndactylies, is clinically heterogeneous. We therefore propose to group the condition into four subtypes, which are all autosomal dominantly inherited. Subtype 1, zygodactyly (cutaneous webbing of second and third toe without hand involvement) is the mildest and most common form.

Autosomal recessive mesoaxial synostotic syndactyly with phalangeal reduction maps to chromosome 17p13.3.

Previously we have described a novel and distinct form of non-syndromic osseous syndactyly segregating in an autosomal recessive pattern in a consanguineous Pakistani family. The limb findings include mesoaxial reduction of the fingers, synostoses of the third and fourth metacarpals with associated single phalanges, fifth finger clinodactyly, and preaxial webbing of toes. We identified another published report of this phenotype in a large, inbred Turkish family.

Public, expert and patients' opinions on preimplantation genetic diagnosis (PGD) in Germany.

The regulation of reproductive medicine technologies differs significantly among Western industrialized countries. In Germany, preimplantation genetic diagnosis (PGD) is prohibited due to the Embryo Protection Act, which came into force in 1991. In the last 5 years, this prohibition has been vigorously debated.

A novel type of autosomal recessive syndactyly: clinical and molecular studies in a family of Pakistani origin.

Non-syndromic syndactylies have been classified into five major types (I-V), all showing autosomal dominant mode of inheritance. Later, the classification was extended and three additional variants (VI-VIII) were defined. Type VII, the Cenani-Lenz syndactyly, is the only non-syndromic, autosomal recessive type.

Muscle pathology in 57 patients with myotonic dystrophy type 2.

We evaluated muscle biopsies from 57 patients with genetically confirmed myotonic dystrophy type 2/proximal myotonic myopathy (DM2/PROMM). Light microscopy showed myopathic together with "denervation-like" changes in almost all biopsies obtained from four different muscles: increased fiber size variation, internal nuclei, small angulated fibers, pyknotic nuclear clumps, and predominant type 2 fiber atrophy. Quantitative morphometry in 18 biopsies that were immunostained for myosin heavy chain confirmed a predominance of nonselective type 2 fiber atrophy.

Facioscapulohumeral muscular dystrophy. Phenotype-genotype correlation in patients with borderline D4Z4 repeat numbers.

Facioscapulohumeral muscular dystrophy (FSHD) is associated with a decreased number of D4Z4 repeats on chromosome 4q35. Diagnostic difficulties arise from atypical clinical presentations and from an overlap in D4Z4 numbers between controls and FSHD individuals. Thus, a molecular genetic test result with a borderline D4Z4 number has its limitations for the clinician wanting to differentiate between the diagnosis of FSHD and a myopathy presenting with FSHD-like symptoms.

Evaluation of BMP4 and its specific inhibitor NOG as candidates in human neural tube defects (NTDs).

Neural tube defects (NTD) are among the most common congenital malformations in humans. The current view is that there are no major genes causing NTDs, but combinations of sequence variants in different genes have additive effects on determining the malformation. Therefore it is important to identify such sequence variants to get a better understanding of NTD pathogenesis.

A polymorphic microsatellite that mediates induction of PIG3 by p53.

The gene PIG3 is induced by the tumor suppressor p53 but not by p53 mutants unable to induce apoptosis, suggesting its involvement in p53-mediated cell death. Here we show that p53 directly binds and activates the PIG3 promoter, but not through the previously described DNA element. Instead, p53 interacts with a pentanucleotide microsatellite sequence within the PIG3 promoter (TGYCC)n where Y=C or T.