6 research outputs found
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
Sarcoglycanopathy: Clinical and histochemical characteristics in 66 patients
Background: Sarcoglycanopathies are a group or autosomal recessive
muscular dystrophies designated as α, β, 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 a-SG deficiency in 7 (10.6%), isolated b-SG deficiency in 6
(9.1%), and isolated g-SG deficiency in 3 (4.5%). Combination
deficiency was also observed: absence of α and β (n=4),
β 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