Résumé :
|
A 10-year-old female child presented with 2-year history of progressive difficulty in walking and getting up from supine posture. Clinical evaluation, serum creatine phosphokinase levels (2222 IU/L) and muscle biopsy was consistent with muscular dystrophy and LGMD was suspected. DMD gene deletion analysis by multiplex PCR was performed at our facility to rule out DMD. Surprisingly, multiplex PCR showed a homozygous deletion of exon 45 of the DMD gene. The gene deletion was confirmed by Multiplex Ligation-Dependent Probe Amplification (MLPA) and dystrophin gene microsatellite marker STR45. This rules out the possibility of skewed X-inactivation to be the cause of her clinical symptoms. Karyotype analysis was normal, ruling out Turner’s syndrome and translocations involving the X-Chromosome. Dystrophin gene microsatellite analysis using STR44 and STR 45 revealed deletion of STR45 and homozygosity for STR44. This homozygosity for STR 44 shows the possibility of the homozygous deletion to be a consequence of Uniparental isodisomy. However, blood samples of the parents of the affected girl are not available at present with us to confirm this phenomenon. Marker studies are in progress to look for disomy of the entire X-chromosome. Duchenne muscular dystrophy (DMD) is X-linked recessive disorder usually affecting males. DMD in females has been described earlier, commonly caused due to skewed X chromosome inactivation or translocations involving the X chromosome at the DMD locus. Females with Turner syndrome (45,X) are affected with DMD if they carry a dystrophin mutation on the remaining X chromosome. Usually girls presenting with a DMD-like dystrophy are diagnosed as having limb girdle dystrophy rather than DMD. Our study shows that these girls need to be evaluated for DMD gene mutations to confirm this diagnosis. There is only one published report of uniparental disomy causing DMD in 1997. Ours would be a second such report, if confirmed for UPD.
|