Large Linkage Analysis in 100 Families with Autosomal Recessive Spinal Muscular Atrophy (SMA) and 11 CEPH Families Using 15 Polymorphic Loci in the Region 5q11.2-q13.3

Wirth, Brunhilde; Pick, Elke; Leutner, Andreas; Dadze, A.; Voosen, B.; Knapp, Michael; Piechaczek-Wappenschmidt, B.; Rudnik‐Schöneborn, Sabine; Schönling, Jutta; Cox, S A; Spurr, N.K.; Zerres, Klaus

doi:10.1006/geno.1994.1130

Cited by 40 publications

(15 citation statements)

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“…A complication/pitfall in the dosimetric analysis of SMN1 exon 7 is the occurrence of two (or more) SMN1 genes on a single chromosome 5 in about 4%, as observed by McAndrew et al, 21 Wirth et al 35 and others. This would bear on the sensitivity of this technique for carrier identification, since individuals with an SMN1 [1,1] genotype (a single SMN1 gene on each chromosome; non-carriers) cannot be distinguished from individuals with an SMN1 [0,2] genotype (both SMN1 genes on a single chromosome; carriers).…”

Section: Carrier Testingmentioning

confidence: 91%

Best practice guidelines for molecular analysis in spinal muscular atrophy

et al. 2001

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Section: Carrier Testingmentioning

confidence: 91%

Best practice guidelines for molecular analysis in spinal muscular atrophy

et al. 2001

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“…The localization of the SMA critical region allowed linkage analysis to be used as the first genetic test for SMA (Brahe et al 1994;Burghes et al 1994;Clermont et al 1994;Daniels et al 1992;Melki et al 1994;Morrison et al 1993;Soares et al 1993;Wirth et al 1994). Centromeric to telomeric, informative linkage markers that have been reported are as follows: D5S679, D5S680, D5S125, D5S681, D5S435, D5S629, D5S823, D5S1556/ D5F150 (intragenic/SMN1 promoter region), D5S149 (intragenic/SMN1 promoter region), (SMN1), D5S557, D5S610, D5S351, 5'-MAP1B, 3'-MAP1B, D5S112, D5S127, and D5S539 (Brahe et al 1994;Burghes et al 1994;Daniels et al 1992;Morrison et al 1993;; for a review, see Scheffer et al 2001).…”

Section: Linkage Analysismentioning

confidence: 99%

Genetic testing and risk assessment for spinal muscular atrophy (SMA)

2002

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Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases, affecting approximately 1 in 10,000 live births, and with a carrier frequency of approximately 1 in 50. Because of gene deletion or conversion, SMN1 exon 7 is homozygously absent in approximately 94% of patients with clinically typical SMA. Approximately 30 small intragenic SMN1 mutations have also been described. These mutations are present in many of the approximately 6% of SMA patients who do not lack both copies of SMN1, whereas SMA of other patients without a homozygous absence of SMN1 is unrelated to SMN1. A commonly used polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) assay can be used to detect a homozygous absence of SMN1 exon 7. SMN gene dosage analyses, which can determine the copy numbers of SMN1 and SMN2 (an SMN1 homolog and a modifier for SMA), have been developed for SMA carrier testing and to confirm that SMN1 is heterozygously absent in symptomatic individuals who do not lack both copies of SMN1. In conjunction with SMN gene dosage analysis, linkage analysis remains an important component of SMA genetic testing in certain circumstances. Genetic risk assessment is an essential and integral component of SMA genetic testing and impacts genetic counseling both before and after genetic testing is performed. Comprehensive SMA genetic testing, comprising PCR-RFLP assay, SMN gene dosage analysis, and linkage analysis, combined with appropriate genetic risk assessment and genetic counseling, offers the most complete evaluation of SMA patients and their families at this time. New technologies, such as haploid analysis techniques, may be widely available in the future.

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“…It is the most common fatal autosomal recessive neurological illness and occurs in three distinct clinical forms differentiated by their severity (12), all linked to the same locus on 5q13 (10,11,13). The repetitive nature and unusual instability of this region hindered the task of narrowing down the critical region and identifying candidate genes (7,8,(14)(15)(16)(17). However, deletions of several regional polymorphic markers in SMA patients (7,9) led to the discovery of three candidate genes, all present in multiple copies and exhibiting homozygous deletions in SMA patients at very high rates (18)(19)(20).…”

mentioning

confidence: 99%

Expressed cadherin pseudogenes are localized to the critical region of the spinal muscular atrophy gene.

Selig

Bruno

Scharf

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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Low-copy repeats have been associated with genomic rearrangements and have been implicated in the generation of mutations in several diseases. Here we characterize a subset of low-copy repeats in the spinal muscular atrophy (SMA) region in human chromosome 5q13. We show that this repeated sequence, named c41-cad, is a highly expressed pseudogene derived from an intact neuronal cadherin gene, Br-cadherin, situated on Spl3-14. Br-cadherin is expressed specifically in the brain, whereas the c41-cad transcripts are 10-15 times more abundant and are present in all tissues examined. We speculate that the c41-cad repeats, separately or in concert with other repeats in the SMA region, are involved in the pathogenesis of SMA by promoting rearrangements and deletions.

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Large Linkage Analysis in 100 Families with Autosomal Recessive Spinal Muscular Atrophy (SMA) and 11 CEPH Families Using 15 Polymorphic Loci in the Region 5q11.2-q13.3

Cited by 40 publications

References 0 publications

Best practice guidelines for molecular analysis in spinal muscular atrophy

Best practice guidelines for molecular analysis in spinal muscular atrophy

Genetic testing and risk assessment for spinal muscular atrophy (SMA)

Expressed cadherin pseudogenes are localized to the critical region of the spinal muscular atrophy gene.

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