Quantitative Analysis of Survival Motor Neuron Copies: Identification of Subtle SMN1 Mutations in Patients with Spinal Muscular Atrophy, Genotype-Phenotype.

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Date of download: 6/9/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Molecular Analysis and Prenatal Prediction of Spinal.

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Quantitative Analysis of Survival Motor Neuron Copies: Identification of Subtle SMN1 Mutations in Patients with Spinal Muscular Atrophy, Genotype-Phenotype Correlation, and Implications for Genetic Counseling Brunhilde Wirth, M. Herz, A. Wetter, S. Moskau, E. Hahnen, S. Rudnik-Schöneborn, T. Wienker, K. Zerres The American Journal of Human Genetics Volume 64, Issue 5, Pages 1340-1356 (May 1999) DOI: 10.1086/302369 Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 1 SMN1 dosage analysis in patients, carriers, and controls. Example of a silver-stained PAA gel of the multiplex competitive PCR of genomic SMN1, SMN2, SMN internal standard, CFTR, and CFTR internal standard (see the Subjects, Material, and Methods section). The American Journal of Human Genetics 1999 64, 1340-1356DOI: (10.1086/302369) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 2 Plot of the SSMN1 values determined in carriers, noncarriers, and patients with SMA who failed to show homozygous absence of SMN1. Circles correspond to one SMN1 copy, triangles to two SMN1 copies, and squares to three SMN1 copies, and the open rhombus represents the values within the uncertain interval between one and two SMN1 copies (0.60–0.75). The average values for one SMN1 and two SMN1 copies are marked with a horizontal line. The American Journal of Human Genetics 1999 64, 1340-1356DOI: (10.1086/302369) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 3 New intragenic SMN1 mutations in patients with SMA. Mutant sequences of patients (upper) a, 3952; b, 19; c, 1927; d, 2833; e, 2598; and control sequences (lower) are shown. Arrows indicate the positions of the mutations. Bars indicate exon-intron boundaries. The American Journal of Human Genetics 1999 64, 1340-1356DOI: (10.1086/302369) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 4 Alu-mediated deletion in patient 4259 with SMA. A, Long-range PCR products between exons 4 and 8 from father (F), mother (M), and patient (P) were separated on ethidium bromide–stained agarose gels. The normal, full-length SMN-PCR product is 10 kb, whereas the deleted product is 3.4 kb. The size marker is the 1-kb ladder (MBI-Fermentas). B, Sequence homology of the Alu-repetitive elements in introns 4 and 6 to the junction fragment of patient 4259 is shown. The deletion breakpoint region is marked with a gray box; the 26-bp core sequence is written in italics and bold letters. The American Journal of Human Genetics 1999 64, 1340-1356DOI: (10.1086/302369) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 5 Restriction digest PCR-based assay for detection of the Y272C mutation. PCR product obtained from DNA of patient 3551, who carries the Y272C mutation, are cut with Tsp45I into 75-bp and 26-bp fragments; individuals without this mutation show a 101-bp uncut PCR fragment on a 3% ethidium bromide–stained agarose gel. The American Journal of Human Genetics 1999 64, 1340-1356DOI: (10.1086/302369) Copyright © 1999 The American Society of Human Genetics Terms and Conditions