Assessment of Nonallelic Genetic Heterogeneity of Chronic (Type II and III) Spinal Muscular Atrophy

Lm, Brzustowicz; Mérette, Chantal; Kleyn, Patrick; Lehner, Thomas; Lh, Castilla; Gk, Penchaszadeh; K, Das; Tl, Munsat; J, Ott; Tc, Gilliam

doi:10.1159/000154164

Cited by 16 publications

(4 citation statements)

References 18 publications

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“…Of the clinical variables assessed, only a significantly higher rate of social affairs phobia distinguished single and comorbid social phobia cases; but half of the comorbid probands also reported this phobia. The observation of considerable transmissional heterogeneity within clinically (phenomenologically) defined groups is consistent with recent studies in other areas of medicine (Coyle and Puttfarcken, 1993;Kmg et al, 1992;Brzustowicz et al, 1993). Nevertheless, further investigation of possible overlap between our family study findings and other previously studied indicators of heterogeneity within social phobia (e.g., generalized vs. non-generalized) (Heimberg et al, 1990;Levin et al, 1993;Mannuzza et al, 1995;Liebowitz, 1993) would be an interesting next step.…”

Section: Discussionsupporting

confidence: 88%

“…G e n e t i c studies indicate considerable causal heterogeneity within descriptively defined diagnostic categories (Hall et al, 1990;Motulsky and Brunzell, 1992;King et al, 1992;Brzustowicz et al, 1993). In some cases several different genotypes result in the same clinical syndrome (e.g., amyotrophic lateral sclerosis, diabetes) (Coyle and Puttfarcken, 1993;Hashimoto et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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Panic disorder and social phobia: Effects of comorbidity on familial transmission

Fyer

Mannuzza

Chapman

et al. 1996

Anxiety

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The aim of this study was to examine effects of comorbidity of panic disorder and social phobia on familial transmission of each of these disorders. Rates of panic disorder and social phobia were compared in directly interviewed relatives of four proband groups: (1) panic disorder, (2) social phobia, (3) panic disorder and social phobia, and (4) never ill controls. Anxiety disorder probands had no additional lifetime anxiety disorder comorbidity. The familial pattern of the comorbid (panic disorder and social phobia) probands resembled that of the panic disorder group: an increased rate of panic disorder but not social phobia as compared to relatives of controls. Relatives of social phobia probands had an increased rate of social phobia but not panic disorder. These data indicate that social phobia in individuals who subsequently develop panic disorder: (1) differs with respect to familial transmission from social phobia which occurs without lifetime anxiety comorbidity; and (2) may be nonfamilial and/or causally related to panic disorder. Additional studies in larger epidemiologic samples are required to assess generalizability of these findings. Anxiety 2:173–178 (1996). © 1996 Wiley‐Liss, Inc.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Panic disorder and social phobia: Effects of comorbidity on familial transmission

Fyer

Mannuzza

Chapman

et al. 1996

Anxiety

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“…SMA is caused by mutations or deletions in the SMN1 gene (Lefebvre et al, 1995). Due to a second, partially functionally copy, named SMN2 , SMA is a disease of low SMN levels, rather than no SMN (Brzustowicz et al, 1993; Rochette et al, 2001). The clinical severity of SMA is categorized into 4 main types, which vary in their time of onset and expected prognosis (reviewed in Boyer et al, 2010).…”

Section: Spinal Muscular Atrophymentioning

confidence: 99%

More than a bystander: the contributions of intrinsic skeletal muscle defects in motor neuron diseases

2013

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Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and spinal-bulbar muscular atrophy (SBMA) are devastating diseases characterized by the degeneration of motor neurons. Although the molecular causes underlying these diseases differ, recent findings have highlighted the contribution of intrinsic skeletal muscle defects in motor neuron diseases. The use of cell culture and animal models has led to the important finding that muscle defects occur prior to and independently of motor neuron degeneration in motor neuron diseases. In SMA for instance, the muscle specific requirements of the SMA disease-causing gene have been demonstrated by a series of genetic rescue experiments in SMA models. Conditional ALS mouse models expressing a muscle specific mutant SOD1 gene develop atrophy and muscle degeneration in the absence of motor neuron pathology. Treating SBMA mice by over-expressing IGF-1 in a skeletal muscle-specific manner attenuates disease severity and improves motor neuron pathology. In the present review, we provide an in depth description of muscle intrinsic defects, and discuss how they impact muscle function in these diseases. Furthermore, we discuss muscle-specific therapeutic strategies used to treat animal models of SMA, ALS, and SBMA. The study of intrinsic skeletal muscle defects is crucial for the understanding of the pathophysiology of these diseases and will open new therapeutic options for the treatment of motor neuron diseases.

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“…Type I (Werdnig-Hoffmann disease) is the most severe form of SMA, with onset at birth or within the first few months of life, and death usually before age 2. Type II is an intermediate form and Type III (Kugelberg-Welander disease) is the mildest form and usually presents after age 24 months.All three types of SMA have been mapped, using linkage analysis, to chromosome region 5q11.2-13.3 [Gilliam et al, 1990;Melki et al, 1990aMelki et al, , 1990bBrzustowicz et al, 1993;Merette et al, 1994]. The search for an SMA-determining gene was complicated by the instability and complexity of the region-a 500-kb inverted duplication-containing repetitive sequence elements, retrotransposon-like sequences, and expressed pseudogenes [Francis et al, 1995;Lewin, 1995;Selig et al, 1995;Rodrigues et al, 1996;Burglen et al, 1997].…”

mentioning

confidence: 99%

Different molecular basis for spinal muscular atrophy in South African black patients

et al. 1999

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Spinal muscular atrophy (SMA) is an autosomal recessive disorder occurring at a rate of between 1/5,000 and 1/10,000 births in most European countries. The phenotype results from the degeneration of the anterior horn cells of the spinal cord, resulting in symmetrical muscle weakness and wasting. The disorder can be classified according to the severity of the disease and the age of onset into three major types. Two candidate SMA genes, NAIP and SMN, isolated from the 5q13 region, have been reported to be homozygously deleted in approximately 30% and >95% of SMA patients, respectively. Black SMA patients have been reported to have facial muscle weakness more commonly. This study aimed to determine the molecular basis of SMA in South African black SMA patients. The SMN gene was found to be homozygously deleted in 65.5% (19/29) of patients, significantly less frequently than in previous studies. Similarly, the NAIP gene was homozygously deleted in a smaller number, 14% (4/29) of patients; 47% (9/19) of SMN deletion patients appeared to have deletions of telomeric exon 7, but not exon 8. In at least six of these patients a gene conversion event has occurred. No detectable deletions were found in 35% (10/29) of patients. Haplotype analysis in the nondeletion patients, using six closely linked markers, provided no evidence for a founder mutation. No mutations were found in exons 3 and intron 6 through exon 8 by sequence analysis of these nondeletion patients. It is proposed that the differences in the SMA phenotype observed in black patients may in part be explained by a different molecular basis.

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Assessment of Nonallelic Genetic Heterogeneity of Chronic (Type II and III) Spinal Muscular Atrophy

Cited by 16 publications

References 18 publications

Panic disorder and social phobia: Effects of comorbidity on familial transmission

Panic disorder and social phobia: Effects of comorbidity on familial transmission

More than a bystander: the contributions of intrinsic skeletal muscle defects in motor neuron diseases

Different molecular basis for spinal muscular atrophy in South African black patients

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