An intronic mutation causes severe LGMD2A in a large inbred family belonging to a genetic isolate in the Alps

Fanin, Marina; Benedicenti, Francesco; Fritegotto, Chiara; Nascimbeni, Annachiara; Peterle, Enrico; Stanzial, Franco; Cristofoletti, A; Castellan, Claudio

doi:10.1111/j.1399-0004.2012.01873.x

Cited by 10 publications

(8 citation statements)

References 4 publications

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“…High frequency of five founder mutations in the calpain gene has been reported from inbred families in Réunion Island, France (19/20 patients)[ 14 ] and a very high frequency of single founder allele from a single large family of 17 patients from the Mocheni population of the Alps. [ 15 ] Two other founder mutations have been known in the calpain gene, one in Germany and the other in Brazil. [ 7 8 ] These reports quote the percentage positivity of the founder alleles to be 8.1% and 24%.…”

Section: Discussionmentioning

confidence: 99%

Limb-girdle muscular dystrophy in the Agarwals: Utility of founder mutations in CAPN3 gene

Khadilkar

Chaudhari

Dastur

et al. 2016

Ann Indian Acad Neurol

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Background and Purpose:Diagnostic evaluation of limb-girdle muscular dystrophy type 2A (LGMD2A) involves specialized studies on muscle biopsy and mutation analysis. Mutation screening is the gold standard for diagnosis but is difficult as the gene is large and multiple mutations are known. This study evaluates the utility of two known founder mutations as a first-line diagnostic test for LGMD2A in the Agarwals.Materials and Methods:The Agarwals with limb-girdle muscular dystrophy (LGMD) phenotype were analyzed for two founder alleles (intron 18/exon 19 c.2051-1G>T and exon 22 c.2338G>C). Asymptomatic first-degree relatives of patients with genetically confirmed mutations and desirous of counseling were screened for founder mutations.Results:Founder alleles were detected in 26 out of 29 subjects with LGMD phenotype (89%). The most common genotype observed was homozygous for exon 22 c.2338 G>C mutation followed by compound heterozygosity. Single founder allele was identified in two. Single allele was detected in two of the five asymptomatic relatives.Conclusion:Eighty-nine percent of the Agarwals having LGMD phenotype have LGMD2A resulting from founder mutations. Founder allele analysis can be utilized as the initial noninvasive diagnostic step for index cases, carrier detection, and counseling.

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Section: Discussionmentioning

confidence: 99%

Limb-girdle muscular dystrophy in the Agarwals: Utility of founder mutations in CAPN3 gene

Khadilkar

Chaudhari

Dastur

et al. 2016

Ann Indian Acad Neurol

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“…For example, there are several founder mutations in the calpain 3 gene, reported from La Reunion Island,8 Northern Indiana,9 10 Basque country, Spain and Brazil,11–13 Japan,14–16 Venetian lagoon,17 Italian Alps18 and western India 19. The knowledge of regional prevalence and existence of founder mutations can help in reaching a quick genetic diagnosis.…”

Section: Clinical Approachmentioning

confidence: 99%

Making sense of the clinical spectrum of limb girdle muscular dystrophies

2018

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The expansion of the spectrum of limb girdle muscular dystrophies (LGMDs) in recent years means that neurologists need to be familiar with the clinical clues that can help with their diagnosis. The LGMDs comprise a group of genetic myopathies that manifest as chronic progressive weakness of hip and shoulder girdles. Their inheritance is either autosomal dominant (LGMD1) or autosomal recessive (LGMD2). Their prevalence varies in different regions of the world; certain ethnic groups have documented founder mutations and this knowledge can facilitate the diagnosis. The clinical approach to LGMDs uses the age at onset, genetic transmission and clinical patterns of muscular weakness. Helpful clinical features that help to differentiate the various subtypes include: predominant upper girdle weakness, disproportionate respiratory muscle involvement, distal weakness, hip adductor weakness, 'biceps lump' and 'diamond on quadriceps' sign, calf hypertrophy, contractures and cardiac involvement. Almost half of patients with LGMD have such clinical clues. Investigations such as serum creatine kinase, electrophysiology, muscle biopsy and genetic studies can complement the clinical examination. In this review, we discuss diagnostic clinical pointers and comment on the differential diagnosis and relevant investigations, using illustrative case studies.

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“…c.550delA mutation is the most common allele in Caucasian populations. [30] Founder effect for the c.550delA mutation has been demonstrated in the Eastern Mediterranean region (Russia, Croatia, Bulgaria, and Northern Italy)[313233343536373839404142] Other rare mutations which have a founder effect in small populations due to cultural inbreeding associated with historical, demographic, or religious factors have been reported in the population of La Reunion Island in the Indian Ocean (c.946-1G>A),[43] in the Old Order Amish community in Northern Indiana in the USA (c.2306G>A),[4445] in the Guipuzcoa region of the Basque Country of Spain and in Brazil (c.2362_2363delAGinsTCATCT),[464748] Japan (c.1795_1796insA),[495051] the Chioggia village in the Venetian lagoon (p.R490Q),[35] the Mocheni population in the Italian Alps (c.1193 + 6T>A),[52] and the Agarwal community in Northern India (p.D780H and c.2099-1G>T). [53] The last one is relevant to India and hence is discussed further.…”

Section: Calpainopathymentioning

confidence: 99%

Limb-girdle muscular dystrophies in India: A review

Khadilkar¹,

Faldu²,

Patil³

et al. 2017

Ann Indian Acad Neurol

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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.

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An intronic mutation causes severe LGMD2A in a large inbred family belonging to a genetic isolate in the Alps

Cited by 10 publications

References 4 publications

Limb-girdle muscular dystrophy in the Agarwals: Utility of founder mutations in CAPN3 gene

Limb-girdle muscular dystrophy in the Agarwals: Utility of founder mutations in CAPN3 gene

Making sense of the clinical spectrum of limb girdle muscular dystrophies

Limb-girdle muscular dystrophies in India: A review

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