Duchenne muscular dystrophy is caused by mutations in the dystrophin-encoding DMD gene. While Duchenne is most commonly caused by large intragenic deletions that cause frameshift and complete loss of dystrophin expression, in-frame deletions in DMD can result in the expression of internally truncated dystrophin proteins and may be associated with a milder phenotype. In this study, we describe two individuals with large in-frame 5\' deletions (exon 3-23 and exon 3-28) that remove the majority of the N-terminal region, including part of the actin binding and central rod domains. Both patients had progressive muscle weakness during childhood but are observed to have a relatively mild disease course compared to typical Duchenne. We show that in muscle biopsies from both patients, truncated dystrophin is expressed at the sarcolemma. We have additionally developed a patient-specific fibroblast-derived cell model, which can be inducibly reprogrammed to form myotubes that largely recapitulate biopsy findings for the patient with the exon 3-23 deletion, providing a culture model for future investigation of this unusual case. We discuss these mutations in the context of previously reported 5\' in-frame DMD deletions and relevant animal models, and review the spectrum of phenotypes associated with these deletions.

OBJECTIVE: We describe a 3-day-old male infant that was operated on for annular pancreas causing duodenal stenosis. The family history revealed that the mother also underwent surgery as a neonate owing to duodenal stenosis with an annular pancreas. The aim of our study was to perform molecular investigations in this rare and familial congenital malformation.
METHODS: We performed high-resolution (180 K) array comparative genomic hybridization using the infant\'s DNA and multiplex ligation-dependent probe amplification (MLPA) using the parents\' and the affected mother\'s siblings\' and parents\' DNA.
RESULTS: Array comparative genomic hybridization revealed previously unreported duplications on chromosome 6q24.2 and 17q22-q23.1, respectively, in the infant\'s DNA, and the latter duplication was also found in the healthy father using MLPA, whereas the affected mother carried the 6q24 duplication (0.7 Mb) containing parts of the utrophin gene. We further performed MLPA analysis of the 6q24 region and found that the clinically unaffected grandfather was a carrier of the microduplication, and so were 2 asymptomatic siblings of the affected mother.
CONCLUSIONS: The 6q24.2 mircoduplication of the utrophin gene is a potential risk factor for the development of annular pancreas, but further studies will clarify the exact role and if this is a true risk factor or a rare normal variant.

Calponin homology domains link many different proteins to the surface of actin filaments. However, details of the structural interactions involved and the methods used to determine them are controversial. In the case of the actin-binding protein utrophin, for example, several models have been proposed for the binding of utrophin\'s calponin homology domains to actin. We review and evaluate these models and their supporting data.