Interfamilial phenotypic heterogeneity in SMARD1

Joseph, Sumy; Robb, Stephanie; Mohammed, Shehla; Lillis, S.; Simonds, Anita K.; Manzur, Adnan; Walter, Susan V.; Wraige, Elizabeth

doi:10.1016/j.nmd.2008.11.013

Cited by 46 publications

(39 citation statements)

References 14 publications

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“…The longest surviving children reported were 13 and 15 years of age, they had profound upper and lower limb muscle and trunk weakness and respiratory compromise. 18,30 Three children have been reported with delayed onset of respiratory distress of between 4 and 10 years old and designated juvenile SMARD1. 18,35,39 IGHMBP2 was Sanger sequenced in a cohort of 85 likely recessive CMT2 families, and CMT exome sequence data was analyzed from the Hussman Institute for Human Genomics.…”

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confidence: 99%

Truncating and Missense Mutations in IGHMBP2 Cause Charcot-Marie Tooth Disease Type 2

Cottenie

Kochański

Jordanova

et al. 2014

The American Journal of Human Genetics

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Using a combination of exome sequencing and linkage analysis, we investigated an English family with two affected siblings in their 40s with recessive Charcot-Marie Tooth disease type 2 (CMT2). Compound heterozygous mutations in the immunoglobulin-helicase-μ-binding protein 2 (IGHMBP2) gene were identified. Further sequencing revealed a total of 11 CMT2 families with recessively inherited IGHMBP2 gene mutations. IGHMBP2 mutations usually lead to spinal muscular atrophy with respiratory distress type 1 (SMARD1), where most infants die before 1 year of age. The individuals with CMT2 described here, have slowly progressive weakness, wasting and sensory loss, with an axonal neuropathy typical of CMT2, but no significant respiratory compromise. Segregating IGHMBP2 mutations in CMT2 were mainly loss-of-function nonsense in the 5' region of the gene in combination with a truncating frameshift, missense, or homozygous frameshift mutations in the last exon. Mutations in CMT2 were predicted to be less aggressive as compared to those in SMARD1, and fibroblast and lymphoblast studies indicate that the IGHMBP2 protein levels are significantly higher in CMT2 than SMARD1, but lower than controls, suggesting that the clinical phenotype differences are related to the IGHMBP2 protein levels.

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mentioning

confidence: 99%

Truncating and Missense Mutations in IGHMBP2 Cause Charcot-Marie Tooth Disease Type 2

Cottenie

Kochański

Jordanova

et al. 2014

The American Journal of Human Genetics

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“…Apart from the classic neonatal/infantile form, there have been only a few reports of unusual late onset or mild presentations [2,20,21]. Although life expectancy is usually very short, the case of a 20 years old man affected by SMARD1 with precocious onset was recently reported [5].…”

Section: Slowly Progressive Formmentioning

confidence: 99%

“…Many authors performed muscle biopsies and histological examinations in SMARD1 patients [4,16,21,22,24,25]. Histological and ultrastructural findings of peripheral nerves (sural and tibial anterior nerves) showed reduced anterior spinal root diameter, reduction of thick myelinated fibers, and some areas with axons reduction [26].…”

Section: Neuropathological Hallmarksmentioning

confidence: 99%

“…However some exception to this rule can exist. In 2009, a case of a sister and a brother with different phenotypes, but with the same compound heterozygous mutation in the IGHMBP2 gene was described [21]. The sister showed delayed motor development along with distal muscle weakness, respiratory impairment after one year of life, repeated pulmonary infections, and feeding difficulties which required a gastrostomy at 13 years.…”

Section: Genetic Background Of Smard1mentioning

confidence: 99%

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The wide spectrum of clinical phenotypes of spinal muscular atrophy with respiratory distress type 1: A systematic review

Porro¹,

Rinchetti²,

Magri³

et al. 2014

Journal of the Neurological Sciences

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“…Considerable variability in the presentation of SMARD1 and its phenotype in childhood has been reported, including cases with severe early infantile onset sensory-motor neuropathy and those with a later, juvenile onset of respiratory failure [9][10][11][12][13][14]. However there are virtually no data on disease course in affected young adults.…”

Section: Introductionmentioning

confidence: 99%