A report on GNE myopathy: Individuals of Rajasthan ancestry share the Roma gene

Khadilkar, Satish V; Nallamilli, Babi Ramesh Reddy; Bhutada, Ashish; Hegde, Madhuri; Gandhi, Khanjan; Faldu, Hinaben Dayalal; Patil, Sharad D.

doi:10.1016/j.jns.2017.02.005

Cited by 15 publications

(14 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This variant has recently been described as the most common variant in Roma of Europe, with an ethnic founder effect ( 66 , 67 ). Our results and previous studies support the current view that Rajasthan in India is the origin of Roma ethnic group of Europe ( 65 ). Moreover, p.V727M is potentially a founder variant in Indian subcontinent since it was seen with high prevalence in our study and previous studies ( 142 – 144 ), and hence this variant is likely present in carriers at higher rates in the north-western areas of Indian subcontinent.…”

Section: Discussionsupporting

confidence: 92%

“…Molecular findings related to GNE-myopathy patients identified in this study have been reported recently (65) with the most common pathogenic variant in our cohort being the c.1760T>C/c.1853T>C (p.I587T/p.I618T). All patients identified with this variant had their ancestry originating in Rajasthan, a province in the north-west part of India, and all belonged to the Maheshwari and Jain ethnic communities of Rajasthan.…”

Section: Discussionsupporting

confidence: 74%

See 1 more Smart Citation

Clinical and Genomic Evaluation of 207 Genetic Myopathies in the Indian Subcontinent

et al. 2020

Self Cite

View full text Add to dashboard Cite

Objective: Inherited myopathies comprise more than 200 different individually rare disease-subtypes, but when combined together they have a high prevalence of 1 in 6,000 individuals across the world. Our goal was to determine for the first time the clinical-and gene-variant spectrum of genetic myopathies in a substantial cohort study of the Indian subcontinent. Methods: In this cohort study, we performed the first large clinical exome sequencing (ES) study with phenotype correlation on 207 clinically well-characterized inherited myopathy-suspected patients from the Indian subcontinent with diverse ethnicities. Results: Clinical-correlation driven definitive molecular diagnosis was established in 49% (101 cases; 95% CI, 42-56%) of patients with the major contributing pathogenicity in either of three genes, GNE (28%; GNE-myopathy), DYSF (25%; Dysferlinopathy), and CAPN3 (19%; Calpainopathy). We identified 65 variant alleles comprising 37 unique variants in these three major genes. Seventy-eight percent of the DYSF patients were homozygous for the detected pathogenic variant, suggesting the need for carrier-testing for autosomal-recessive disorders like Dysferlinopathy that are common in India. We describe the observed clinical spectrum of myopathies including uncommon and rare subtypes in India:

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 74%

Clinical and Genomic Evaluation of 207 Genetic Myopathies in the Indian Subcontinent

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…have recently documented an interesting occurrence of homozygous mutation c.1853T>C (p.I618T) (24.5%) in Rajasthani Jain and Maheshwari communities: a founder mutation encountered exclusively in European Roma Gypsies. [82] This observation further strengthens the view that European Roma Gypsies originated from Northwestern India.…”

Section: Gne (Udp-n-acetylglucosamine 2-epimerase/n-acetylmannosaminesupporting

confidence: 77%

“…Data from Mumbai also document GNE myopathy, with genetic peculiarities in the people with Rajasthan ancestry. [82]…”

Section: Gne (Udp-n-acetylglucosamine 2-epimerase/n-acetylmannosaminementioning

confidence: 99%

Limb-girdle muscular dystrophies in India: A review

Khadilkar¹,

Faldu²,

Patil³

et al. 2017

Ann Indian Acad Neurol

View full text Add to dashboard Cite

Limb-girdle muscular dystrophies (LGMDs) are common in India. Information on LGMDs has been gradually evolving in the recent years. This information is scattered in case series and case studies. The aim of this study is to collate available Indian information on LGMDs and put it in perspective. PubMed search using keywords such as limb-girdle muscular dystrophies in India, sarcoglycanopathies, dysferlinopathy, calpainopathy, and GNE myopathy was carried out. The published information on LGMDs in Indian context suggests that dysferlinopathy, calpainopathy, sarcoglycanopathies, and other myopathies such as GNE myopathy are frequently seen in India. Besides these, anecdotal reports of many other forms are available, some with genetic support and others showing immunocytochemical defects. The genotypic information on LGMDs is gradually evolving and founder mutations have been detected in selected populations. Further multicenter studies are necessary to document the incidence and prevalence of these common conditions in India.

show abstract

“…2) and may aid in the identification of the site of muscle biopsy. Genetic testing is unlikely to be performed unless there is clinical suspicion, although more patients are being identified by neuromuscular genetic testing panels that include GNE or next-generation (including exome) sequencing [16,73,74].…”

Section: Diagnosismentioning

confidence: 99%

GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges

2018

View full text Add to dashboard Cite

GNE myopathy, previously known as hereditary inclusion body myopathy (HIBM), or Nonaka myopathy, is a rare autosomal recessive muscle disease characterized by progressive skeletal muscle atrophy. It has an estimated prevalence of 1 to 9:1,000,000. GNE myopathy is caused by mutations in the GNE gene which encodes the rate-limiting enzyme of sialic acid biosynthesis. The pathophysiology of the disease is not entirely understood, but hyposialylation of muscle glycans is thought to play an essential role. The typical presentation is bilateral foot drop caused by weakness of the anterior tibialis muscles with onset in early adulthood. The disease slowly progresses over the next decades to involve skeletal muscles throughout the body, with relative sparing of the quadriceps until late stages of the disease. The diagnosis of GNE myopathy should be considered in young adults presenting with bilateral foot drop. Histopathologic findings on muscle biopsies include fiber size variation, atrophic fibers, lack of inflammation, and the characteristic Brimmed^vacuoles on modified Gomori trichome staining. The diagnosis is confirmed by the presence of pathogenic (mostly missense) mutations in both alleles of the GNE gene. Although there is no approved therapy for this disease, preclinical and clinical studies of several potential therapies are underway, including substrate replacement and gene therapy-based strategies. However, developing therapies for GNE myopathy is complicated by several factors, including the rare incidence of disease, limited preclinical models, lack of reliable biomarkers, and slow disease progression.

show abstract

A report on GNE myopathy: Individuals of Rajasthan ancestry share the Roma gene

Cited by 15 publications

References 4 publications

Clinical and Genomic Evaluation of 207 Genetic Myopathies in the Indian Subcontinent

Clinical and Genomic Evaluation of 207 Genetic Myopathies in the Indian Subcontinent

Limb-girdle muscular dystrophies in India: A review

GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges

Contact Info

Product

Resources

About