Genotype-Phenotype Correlation in Chinese Patients with Spinal and Bulbar Muscular Atrophy

<div><p>Spinal and bulbar muscular atrophy (SBMA) is an X-linked recessive motor neuron disease characterized by slowly progressive weakness and atrophy of proximal limbs and bulbar muscles. To assess the genotype-phenotype correlation in Chinese patients, we identified 155 patients with SBMA and retrospectively examined available data from laboratory tests and neurophysiological analyses. Correlations between genotype and phenotype were analyzed. There was an inverse correlation between the length of CAG repeats and age at first muscle weakness (<i>p<0</i>.<i>0001</i>). The serum creatine kinase level showed a significant inverse correlation with disease duration and the age at examination (<i>p=0</i>.<i>019</i> and <i>p=0</i>.<i>004</i>, respectively). Unlike previous classification of motor- and sensory-dominant phenotypes, all findings of nerve conduction, except the amplitudes of median nerve compound motor action potential, were positively correlated to the length of CAG repeats. A significant decline in sensory nerve action potential amplitudes may assist differential diagnosis of SBMA.</p></div

Relationship between the number of CAG repeats and the age at first muscle weakness.

<p>There is an inverse relationship between the number of CAG repeats and the age at first muscle weakness (R² = 0.34, <i>p<0</i>.<i>0001</i>).</p

Demographics of spinal and bulbar muscular atrophy (SBMA) patients.

<p>Demographics of spinal and bulbar muscular atrophy (SBMA) patients.</p

Analysis of nerve conduction in spinal and bulbar muscular atrophy (SBMA) patients.

<p>*Sural SNAP may be absent in patients over 60 years, thus patients over 60 years were excluded.</p><p>Analysis of nerve conduction in spinal and bulbar muscular atrophy (SBMA) patients.</p

Symptoms and onset distribution in 155 SBMA patients.

<p>Clinical symptoms were collected when the patients first came to the clinic. Some patients were presenting more than one symptom. Distribution of first muscle weakness noted as “Both arm & leg” means the patients could hardly recognise the earliest onset muscle.</p><p>Symptoms and onset distribution in 155 SBMA patients.</p

The distribution of the CAG repeats in 2006 wild-type chromosomes.

<p>The distribution of the CAG repeats in 2006 wild-type chromosomes.</p

The single-strand conformation polymorphism analysis of PCR products in A⁶⁶⁹TG/G⁶⁶⁹TG.

<p>Lanes 1–7 were PCR products from different individuals.</p

Detection of the haplotypes defined by C⁹⁸⁷GG/G⁹⁸⁷GG and TAA¹¹¹⁸/TAC¹¹¹⁸ via agarose gel electrophoresis (A) and polyacrylamide gel electrophoresis (B). Lanes 1–4, 5–8 and 9–12 in A and B were PCR products from 6 different individuals.

<p>Detection of the haplotypes defined by C⁹⁸⁷GG/G⁹⁸⁷GG and TAA¹¹¹⁸/TAC¹¹¹⁸ via agarose gel electrophoresis (A) and polyacrylamide gel electrophoresis (B). Lanes 1–4, 5–8 and 9–12 in A and B were PCR products from 6 different individuals.</p

The polyacrylamide gel electrophoresis analysis of ANs and the CAG repeat ladder.

<p>Lanes 1–6 and 8–12 were ANs; lane 7 was the CAG repeat ladder. The CAG repeat numbers of the ladder’s bands were 13, 14, 18–43, 45, 46, 48 and 49. The bands contained 14, 18, 22, 26, 30, 34, 38, 46, 48 and 49 CAG repeats were marked by specific number.</p

The distribution of the haplotypes defined by C⁹⁸⁷GG/G⁹⁸⁷GG and TAA¹¹¹⁸/TAC¹¹¹⁸ according to CAG repeat number.

<p>The distribution of the haplotypes defined by C⁹⁸⁷GG/G⁹⁸⁷GG and TAA¹¹¹⁸/TAC¹¹¹⁸ according to CAG repeat number.</p