Clinical, genetic profile and disease progression of sarcoglycanopathies in a large cohort from India: high prevalence of SGCB c.544A &gt; C

Bardhan, Mainak; Anjanappa, Ram Murthy; Polavarapu, Kiran; Preethish‐Kumar, Veeramani; Vengalil, Seena; Nashi, Saraswati; Sanga, Shamita; Padmanabh, Hansashree; Valasani, Ravi Kiran; Nishadham, Vikas; Keerthipriya, Muddasu; Geetha, Thenral S; Ramprasad, Vedam; Arunachal, Gautham; Thomas, Priya Treesa; Acharya, Moulinath; Nalini, Atchayaram

doi:10.1007/s10048-022-00690-9

Cited by 8 publications

(11 citation statements)

References 65 publications

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“…The SGCB p.Thr182Pro variant is more frequent and is present in 146 (12.5%). This variant was also reported in our recent study [13].…”

Section: Discussionsupporting

confidence: 90%

“…Furthermore, we perform an additional analysis of patients carrying SGCB p.Thr182Pro, which is the more frequent pathogenic variant identified in our study cohort. The SGCB variant was also reported to be the most frequent in our recent study with different sarcoglycanopathies [13]. Analysis identified a large ROH region shared across the patients with SGCB p.Thr182Pro variant.…”

Section: Introductionmentioning

confidence: 62%

“…Available studies on sarcoglycanopathies from India have been largely based on immunocytochemical characterization. Even though in recent years genetic analysis of LGMDs has increasingly been undertaken in various parts of India, there are only a few genetically confirmed SG patients with one small series and some case reports available [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…This variant was found in 146 (12.5%) patients, and in 142 (97.9%) of them, it was found to be homozygous. We recently published this variant in our study on 20 patients, and it was also reported as one of the most frequent variants [13]. To investigate the patients with SGCB p.Thr182Pro variant, we performed whole genome Human Mutation array genotyping and analysis to understand the founder event, which is described below.…”

mentioning

confidence: 99%

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Large Region of Homozygous (ROH) Identified in Indian Patients with Autosomal Recessive Limb-Girdle Muscular Dystrophy with p.Thr182Pro Variant in SGCB Gene

Manjunath

Thenral

Lakshmi³

et al. 2023

Human Mutation

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The sarcoglycanopathies are autosomal recessive limb-girdle muscular dystrophies (LGMDs) caused by the mutations in genes encoding the α, β, γ, and δ proteins which stabilizes the sarcolemma of muscle cells. The clinical phenotype is characterized by progressive proximal muscle weakness with childhood onset. Muscle biopsy findings are diagnostic in confirming dystrophic changes and deficiency of one or more sarcoglycan proteins. In this study, we summarized 1,046 LGMD patients for which a precise diagnosis was identified using targeted sequencing. The most frequent phenotypes identified in the patients are LGMDR1 (19.7%), LGMDR4 (19.0%), LGMDR2 (17.5%), and MMD1 (14.5%). Among the reported genes, each of CAPN3, SGCB, and DYSF variants was reported in more than 10% of our study cohort. The most common variant SGCB p.Thr182Pro was identified in 146 (12.5%) of the LGMD patients, and in 97.9% of these patients, the variant was found to be homozygous. To understand the genetic structure of the patients carrying SGCB p.Thr182Pro, we genotyped 68 LGMD patients using a whole genome microarray. Analysis of the array data identified a large ~1 Mb region of homozygosity (ROH) (chr4:51817441-528499552) suggestive of a shared genomic region overlapping the recurrent missense variant and shared across all 68 patients. Haplotype analysis identified 133 marker haplotypes that were present in ~85.3% of the probands as a double allele and absent in all random controls. We also identified 5 markers (rs1910739, rs6852236, rs13122418, rs13353646, and rs6554360) which were present in a significantly higher proportion in the patients compared to random control set ( n = 128 ) and the population database. Of note, admixture analysis was suggestive of greater proportion of West Eurasian/European ancestry as compared to random controls. Haplotype analysis and frequency in the population database indicate a probable event of founder effect. Further systematic study is needed to identify the communities and regions where the SGCB p.Thr182Pro variant is observed in higher proportions. After identifying these communities and//or region, a screening program is needed to identify carriers and provide them counselling.

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“…The SGCB p.Thr182Pro variant is more frequent and is present in 146 (12.5%). This variant was also reported in our recent study [13].…”

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Large Region of Homozygous (ROH) Identified in Indian Patients with Autosomal Recessive Limb-Girdle Muscular Dystrophy with p.Thr182Pro Variant in SGCB Gene

Manjunath

Thenral

Lakshmi³

et al. 2023

Human Mutation

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“…Among SGCG mutation, 525delT was encountered in 50% of the cases although haplotype analysis has not been undertaken. Recently, Bardhan et al 8 investigated the clinical picture, genetic basis, and disease progression of 68 patients genetically confirmed to have SG. The most common mutation identified was c.544 T > G in SGCB detected in 20 patients (29.42%) from the southern states of Tamil Nadu, Karnataka and Andhra Pradesh in India indicating a founder event leading to the descend of this mutation from a common ancestor.…”

Section: Introductionmentioning

confidence: 99%

Identification of a shared, common haplotype segregating with an SGCB c.544 T > G mutation in Indian patients affected with sarcoglycanopathy

Sanga,

Chakraborty,

Bardhan

et al. 2023

Sci Rep

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Sarcoglycanopathy is the most frequent form of autosomal recessive limb-girdle muscular dystrophies caused by mutations in SGCB gene encoding beta-sarcoglycan proteins. In this study, we describe a shared, common haplotype co-segregating in 14 sarcoglycanopathy cases from 13 unrelated families from south Indian region with the likely pathogenic homozygous mutation c.544 T > G (p.Thr182Pro) in SGCB. Haplotype was reconstructed based on 10 polymorphic markers surrounding the c.544 T > G mutation in the cases and related family members as well as 150 unrelated controls from Indian populations using PLINK1.9. We identified haplotype H1 = G, A, G, T, G, G, A, C, T, G, T at a significantly higher frequency in cases compared to related controls and unrelated control Indian population. Upon segregation analysis within the family pedigrees, H1 is observed to co-segregate with c.544 T > G in a homozygous state in all the pedigrees of cases except one indicating a probable event of founder effect. Furthermore, Identical-by-descent and inbreeding coefficient analysis revealed relatedness among 33 new pairs of seemingly unrelated individuals from sarcoglycanopathy cohort and a higher proportion of homozygous markers, thereby indicating common ancestry. Since all these patients are from the south Indian region, we suggest this region to be a primary target of mutation screening in patients diagnosed with sarcoglycanopathy.

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Phenotype-genotype spectrum of a cohort of congenital muscular dystrophies: a single-centre experience from India

Chawla,

Nashi,

Baskar

et al. 2024

Neurogenetics

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Clinical, genetic profile and disease progression of sarcoglycanopathies in a large cohort from India: high prevalence of SGCB c.544A > C

Cited by 8 publications

References 65 publications

Large Region of Homozygous (ROH) Identified in Indian Patients with Autosomal Recessive Limb-Girdle Muscular Dystrophy with p.Thr182Pro Variant in SGCB Gene

Large Region of Homozygous (ROH) Identified in Indian Patients with Autosomal Recessive Limb-Girdle Muscular Dystrophy with p.Thr182Pro Variant in SGCB Gene

Identification of a shared, common haplotype segregating with an SGCB c.544 T > G mutation in Indian patients affected with sarcoglycanopathy

Phenotype-genotype spectrum of a cohort of congenital muscular dystrophies: a single-centre experience from India

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