Sarcoglycanopathy: clinical and histochemical characteristics in 66 patients.

BACKGROUND: Sarcoglycanopathies are a group or autosomal recessive muscular dystrophies designated as α, ß, γ, or δ sarcogycanopathy. MATERIALS AND METHODS: It is a retrospective analysis of case series. RESULTS: Sixty six patients immunohistochemically confirmed to have sarcoglycan deficiency were included in the analysis. The study period extended from 1997-2008. The male to female ratio was 1.5:1. Mean age at the onset of muscle complaints was 6.2±3.7 years (range 1-18). Mean age at evaluation was 10.0±4.8 years (range 3-31). Mean duration of illness was 47.02±44.80 months (range 3-325). Onset in the first decade was seen in 59 (89.4%) and 25 (42.4%) of these had onset before five years of age. The remaining seven (10.6%) had onset in second decade and none after 20 years of age. Consanguinity was present in 54 (81.8%). In 34 of 66 cases only a-SG was carried out and this had shown total absence of staining in all fibers. In the remaining 32 cases where the entire panel was performed, absence of all sarcoglycans was noted in 10 (15.1%), isolated α-SG deficiency in 7 (10.6%), isolated ß-SG deficiency in 6 (9.1%), and isolated γ-SG deficiency in 3 (4.5%). Combination deficiency was also observed: absence of α and ß (n=4), ß and γ (n=2), and α and γ (n=1). CONCLUSIONS: Our series was a large series and with predominantly pediatric age group. Sarcoglycanopathy should be particularly suspected in a child born to consanguineous parents and who presents with proximal muscle weakness and calf hypertrophy, elevated CK level, and myopathic pattern on EMG.

Duchenne muscular dystrophy: a clinical, histopathological and genetic study at a neurology tertiary care center in Southern India.

BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy that affects young boys and the dystrophin gene on the X chromosome has been found to be associated with the disorder. MATERIALS AND METHODS: In this prospective study, 112 clinically diagnosed DMD patients had muscle biopsy and were tested for exon deletions. Genotyping was also carried out at STR44, STR45, STR49 and STR 50 markers in 15 families. RESULTS: Of the 112 clinically suspected DMD patients, the diagnosis of DMD was confirmed by histopathology and/or genetics in 101 patients. The mean age of onset was 3.1+/-1.44 years (1-6 years) and the mean age at presentation was 8.0+/-3.1 years (1.1-18.0 years). Delayed motor milestones were present in 63 (62.3%) patients. The mean creatine kinase value was 11822.64+/-8206.90 U/L (1240-57,700). Eighty-four patients had muscle biopsy and immunohistochemistry was done in 60 muscle samples, all of which demonstrated absence of dystrophin staining. Of the 60 dystrophin-negative cases, 73% showed deletion of at least one exon. Single exon deletion was found in 20.4%. Distal hotspot Exons 45, 47, 49 and 50 were the commonly deleted xenons and the deletion rates were 36%, 35%, 33.7% and 38.5% respectively. CONCLUSIONS: In this study population in south India the deletion rate was 73% and were more frequent in the distal end exon. With the availability of genetic analysis, the first investigation of choice in DMD should be genetic studies and muscle biopsy should be considered only if the genetic tests are negative or not available.

Deletion analysis of spinal muscular atrophy in southern Indian population.

BACKGROUND: Proximal spinal muscular atrophy (SMA) is a genetically heterogeneous disease with paresis and muscle atrophy due to loss of anterior horn cell function. The survival of motor neuron gene (SMN) and neuronal apoptosis inhibitory protein (NAIP) play a primary role. Both the gene homologues exist as inverted duplications on Chromosome 5q. The telomeric/functional (SMN1) and the centromeric (SMN2) copies differ from each other in eight nucleotides. The C-->T transition (at Codon 280) within Exon 7 of SMN2 causes disruption of an exonic splicing enhancer (ESE) and/or creates an exonic splicing silencer (ESS) leading to abnormal splicing and a truncated protein. OBJECTIVE: To determine the molecular genetics of SMN1 and NAIP genes in SMA from southern India. MATERIALS AND METHODS: In the present study, 37 patients from the neuromuscular disorders clinic of National Institute of Mental Health and Neurosciences were assayed for the deletions in the SMN1 and NAIP genes using PCR-RFLP methods. RESULTS: Among the SMA Type I patients, 43% showed deletions of SMN1 and NAIP. In patients Type II SMA, 57% showed deletions of the SMN1 exons. CONCLUSION: Thus, deletions were found to occur in 47.8% of the Type I and II patients. Lower sensitivity of gene deletion study in clinically suspected SMA needs further study as clinical diagnosis of SMA is not gold standard. However, the results do correlate with other studies conducted in India.