NKX2-5 is a homeodomain-containing transcription factor important in cardiac development. Familial mutations in the NKX2-5 gene are associated with cardiac abnormalities, but mutations are rare in sporadic cases. We studied the pathology and molecular genetics of NKX2-5 in diseased heart tissues of 68 patients with complex congenital heart disease (CHD), particularly atrial (ASD), ventricular (VSD), and atrioventricular septal defects (AVSD). We also studied DNA extracted from 16 normal hearts, as well as lymphocytic DNA from 50 healthy volunteers, 7 families, and 4 unrelated individuals with CHD. Direct sequencing revealed 53 NKX2-5 mutations in the diseased heart tissues, including nonsynonymous substitutions in the homeodomain of NKX2-5. We found common mutations among unrelated patients, but certain mutations were specific to VSDs and AVSDs. Many patients had multiple NKX2-5 mutations, up to 14 nonsynonymous mutations per patient in VSDs. Importantly, these nonsynonymous mutations were mainly absent in normal heart tissues of the same CHD patients, thus indicating somatic origin and mosaicism of mutations. Further, observed mutations were completely absent in normal hearts and lymphocytic DNA of healthy individuals. Our findings provide new insights for somatic NKX2-5 mutations to be of importance in congenital heart disease.

The congruency of the joint surface can not be restored to the original status, particularly in larger defects with irregular shapes. However, we did not find any aspects which affected the function of the knee joint following OCT. It can be assumed that remaining lesions at the surrounding cartilage could maintain the inflammatory process and therefore maintain the pain and a low knee function. Further investigations are needed to specify the effects of the OCT on the transplanted cartilage and its influence on the later clinical outcome.

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OBJECTIVE To estimate the morphological suitability of human connective tissue structures from different regions as graft material in Peyronie's disease, and to present preliminary results from 12 patients with grafting of corporal bodies using autologous rectus sheath. PATIENTS AND METHODS In five male cadavers the penile tunica albuginea was compared with the dorsal lamina of the rectus sheath, the palmar aponeurosis, the iliotibial tract and the Achilles tendon by using histological sections stained with haematoxylin and eosin, Crossmon's trichrome stain and resorcin‐fuchsin. Surgical results and complication rates were investigated in 12 patients with Peyronie's disease after grafting the corporal bodies with autologous rectus sheath to correct their penile curvature. RESULTS On histology, the penile tunica albuginea showed a three‐dimensional meshwork of collagenous and elastic fibres. The dorsal lamina of the rectus sheath had a remarkably similar fibre structure. The other tissues had a different histology, with long collagenous fibres in parallel orientation and elastic fibres restricted to the loose connective tissue around blood vessels and nerves. Clinically, the penile deviation was successfully corrected in 10 patients; there were two residual deviations (15° and 35°). There were minor complications after surgery in six patients, not requiring surgery. CONCLUSIONS The dorsal lamina of the rectus sheath has similar morphological characteristics to the tunica albuginea, and therefore represents an ideal autologous graft; the first clinical results are promising.

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