Early Onset of Sleep-Disordered Breathing in Two Children With SEPN1-Related Myopathies.

ABSTRACT: Selenoprotein-related myopathy (SEPN1-RM) is a rare disease with a variable clinical presentation. The selenoprotein N1 gene (SEPN1) mutation causing this congenital muscular dystrophy was identified in 2001. Sleep-disordered breathing (SDB) may occur in young patients with SEPN1-RM who are still able to walk. We report the cases of two children with SEPN1-RM who presented with SDB at the ages of 7 and 12 years and for whom long-term nocturnal noninvasive ventilation yielded significant improvement. Based on literature review and our current cases, it seems that there is no obvious relationship between the time since SDB onset and outcome of pulmonary function tests or limb muscle weakness. We therefore suggest that SDB should be systematically screened for in patients with SEPN1-RM, at regular intervals using nocturnal polysomnography.

Novel mutational mechanism in the thyroglobulin gene: imperfect DNA inversion as a cause for hereditary hypothyroidism.

The objective of this study was to perform genetic analysis in three brothers of Turkish origin born from consanguineus parents and affected by congenital hypothyroidism, goiter and low levels of serum TG. The combination of sequencing of DNA, PCR mapping, quantitative real-time PCR, inverse-PCR (I-PCR), multiplex PCR and bioinformatics analysis were used in order to detect TG mutations. We demonstrated that the three affected siblings are homozygous for a DNA inversion of 16,962bp in the TG gene associated with two deleted regions at both sides of the inversion limits. The inversion region includes the first 9bp of exon 48, 1015bp of intron 47, 191bp of exon 47, 1523bp of intron 46, 135bp of exon 46 and the last 14,089bp of intron 45. The proximal deletion corresponds to 27bp of TG intron 45, while the distal deletion spans the last 230bp of TG exon 48 and the first 588bp of intergenic region downstream TG end. The parents were heterozygous carriers of the complex rearrangement. In conclusion, a novel large imperfect DNA inversion within the TG gene was identified by the strategy of I-PCR. This aberration was not detectable by normal sequencing of the exons and exon/intron boundaries. Remarkably, the finding represents the first description of a TG deficiency disease caused by a DNA inversion.