The Gene Frequency of Acute Werdnig-Hoffmann Disease (SMA Type 1). A Total Population Survey in North-East England

Pearn, John

doi:10.1136/jmg.10.3.260

Cited by 144 publications

(67 citation statements)

References 14 publications

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“…The risk of OBPP is increased by high birth weight [43,44] and by the presence of shoulder dystocia [45]. OBPP injury occurs more commonly to the upper roots C5 and C6 (Duchenne-Erbs's palsy), and Klumpke's palsy involving C8 and T1 roots is less common.…”

Section: Discussionmentioning

confidence: 99%

A Case of Congenital Bilateral Absence of Elbow Flexor Muscles: Review of Differential Diagnosis and Treatment

Netscher

Aliu

Samra

et al. 2007

Hand (New York, N,Y.)

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A 1-year-old boy presented to us with congenital inability to flex his elbow. He had bilaterally absent biceps brachii and brachialis muscles, a rare condition. We performed pedicle latissimus dorsi musculocutaneous flaps to the left and right volar upper arm at 21 and 24 months of age, respectively, to create elbow flexors. By 4 years of age, he had excellent elbow flexion bilaterally with strength grade in excess of 4.5. In addition to discussing our patient's treatment options, we discuss other potential causes of weak elbow flexion when faced with this clinical dilemma.

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Section: Discussionmentioning

confidence: 99%

A Case of Congenital Bilateral Absence of Elbow Flexor Muscles: Review of Differential Diagnosis and Treatment

Netscher

Aliu

Samra

et al. 2007

Hand (New York, N,Y.)

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“…[2][3][4][5][6][7][8][9][10][11][12] 5q-SMA has an incidence of 1/10,000 with an estimated carrier frequency of 1/50. [13][14][15][16][17] Deletion and gene conversion events result in a 95% to 98% rate of homozygous loss of the SMN1 gene in patients with classic SMA. 1,18 -31 A further 1% to 3% of well-characterized SMA cases are the result of compound heterozygosity with an intragenic mutation and a deletion.…”

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confidence: 99%

Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2

Mailman

Heinz

Papp

et al. 2002

Genetics in Medicine

324

220

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Purpose: This study describes SMN1 deletion frequency, carrier studies, and the effect of the modifying SMN2 gene on the spinal muscular atrophy (SMA) phenotype. A novel allele-specific intragenic mutation panel increases the sensitivity of SMN1 testing. Methods: From 1995 to 2001, 610 patients were tested for SMN1 deletions and 399 relatives of probands have been tested for carrier status. SMN2 copy number was compared between 52 type I and 90 type III patients, and between type I and type III patients with chimeric SMN genes. A fluorescent allele-specific polymerase chain reaction (PCR) -based strategy detected intragenic mutations in potential compound heterozygotes and was used on 366 patients. Results: Less than half of the patients tested were homozygously deleted for SMN1. A PCR-based panel detected the seven most common intragenic mutations. SMN2 copy number was significantly different between mild and severely affected patients. Conclusions: SMN1 molecular testing is essential for the diagnosis of SMA and allows for accurate carrier testing.Screening for intragenic mutations in SMN1 increases the sensitivity of diagnostic testing. Finally, SMN2 copy number is conclusively shown to ameliorate the phenotype and provide valuable prognostic information. Genet Key Words: spinal muscular atrophy, SMN, polymerase chain reactionSpinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by homozygous mutation of the SMN1 gene 1 on chromosome 5q13. 2-12 5q-SMA has an incidence of 1/10,000 with an estimated carrier frequency of 1/50. [13][14][15][16][17] Deletion and gene conversion events result in a 95% to 98% rate of homozygous loss of the SMN1 gene in patients with classic SMA. 1,18 -31 A further 1% to 3% of well-characterized SMA cases are the result of compound heterozygosity with an intragenic mutation and a deletion. 31,32 Clinically, SMA patients are classified as type I, II, or III, based on the severity of the disease and the age of onset. 33,34 SMA type I, also known as Werdnig-Hoffmann disease, 35,36 is the most severe presentation. Type I infants are hypotonic and have severe proximal muscle wasting due to a lack of ␣-motor neurons in the anterior horn of the spinal cord. These patients are diagnosed prenatally or within 6 months after birth. They never sit unaided and usually die within the first 2 years, most often due to respiratory muscle weakness. Patients with intermediate SMA type II develop the disease before 18 months of age. They are able to sit unaided, but do not stand or walk. SMA type III, also called Kugelberg-Welander disease, is less severe. 37,38 Type III patients are diagnosed after 18 months, are able to walk, can have children, and often live at least into the second or third decade. 39 This study presents the clinical experience of 6 years of SMA testing in the Molecular Pathology Laboratory at The Ohio State University. Despite the fact that more than 95% of 5q-linked SMA patients lack any intact SMN1, it has been our experience that Ͻ43% of patients ...

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“…Affecting 1 in 6-10,000 and with a carrier frequency of approximately 1 in 40, SMA is one of the leading genetic causes of infant mortality [1,58,59]. Loss of anterior horn lower motor neurons, the classic hallmark of SMA, leads to proximal muscle weakness, with subsequent paralysis and premature death in more severe cases.…”

Section: Spinal Muscular Atrophymentioning

confidence: 99%

C. elegans models of neuromuscular diseases expedite translational research

Sleigh

Sattelle²

2010

Translational Neuroscience

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The nematode Caenorhabditis elegans is a genetic model organism and the only animal with a complete nervous system wiring diagram. With only 302 neurons and 95 striated muscle cells, a rich array of mutants with defective locomotion and the facility for individual targeted gene knockdown by RNA interference, it lends itself to the exploration of gene function at nerve muscle junctions. With approximately 60% of human disease genes having a C. elegans homologue, there is growing interest in the deployment of lowcost, high-throughput, drug screens of nematode transgenic and mutant strains mimicking aspects of the pathology of devastating human neuromuscular disorders. Here we explore the contributions already made by C. elegans to our understanding of muscular dystrophies (Duchenne and Becker), spinal muscular atrophy, amyotrophic lateral sclerosis, Friedreich’s ataxia, inclusion body myositis and the prospects for contributions to other neuromuscular disorders. A bottleneck to low-cost, in vivo, large-scale chemical library screening for new candidate therapies has been rapid, automated, behavioural phenotyping. Recent progress in quantifying simple swimming (thrashing) movements is making such screening possible and is expediting the translation of drug candidates towards the clinic.

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The Gene Frequency of Acute Werdnig-Hoffmann Disease (SMA Type 1). A Total Population Survey in North-East England

Cited by 144 publications

References 14 publications

A Case of Congenital Bilateral Absence of Elbow Flexor Muscles: Review of Differential Diagnosis and Treatment

A Case of Congenital Bilateral Absence of Elbow Flexor Muscles: Review of Differential Diagnosis and Treatment

Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2

C. elegans models of neuromuscular diseases expedite translational research

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