Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy

Senderek, Jan; Krieger, Michael J. B.; Stendel, Claudia; Bergmann, Carsten; Moser, Markus; Breitbach-Faller, N.; Rudnik‐Schöneborn, Sabine; Blaschek, Astrid; Wolf, Nicole I.; Harting, Inga; North, Klaus; Smith, Janine; Muntoni, F.; Brockington, M; Quijano‐Roy, Susana; Renault, Francis; Herrmann, Ralf; Hendershot, Linda M.; Schröder, Johann Michael; Lochmüller, Hanns; Topaloğlu, Haluk; Voit, T.; Weis, Joachim; Ebinger, Friedrich; Zerres, Klaus

doi:10.1038/ng1678

Cited by 230 publications

(212 citation statements)

References 12 publications

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“…Thus, the loss of SIL1 protein function results in BiP recycling and the accumulation of unfolded proteins in the endoplasmic reticulum. [11][12][13] Senderek et al 5 were unable to identify any SIL1 gene mutations in four individuals with typical MSS. These reports suggested genetic heterogeneity in MSS or that individuals exhibiting MSS may contain mutations that are difficult to detect.…”

Section: Discussionmentioning

confidence: 97%

“…The mutation we found was located in exon 6, which encodes the BiP-interacting domain. 5 Zhao et al 11 have reported that the SIL1 protein associates with the BiP chaperone to aid unfolded proteins in folding normally, and to help in the release of folded proteins. Thus, the loss of SIL1 protein function results in BiP recycling and the accumulation of unfolded proteins in the endoplasmic reticulum.…”

Section: Discussionmentioning

confidence: 99%

“…Two years later, two groups independently identified several mutations in the SIL1 gene located at chromosome 5q31 in MSS. In addition, Senderek et al 5 identified nine different mutations in eight MSS families, and Anttonen et al 6 found four different mutations in eight MSS families. Further novel mutations in the SIL1 gene in MSS were subsequently identified.…”

Section: Introductionmentioning

confidence: 99%

“…Further novel mutations in the SIL1 gene in MSS were subsequently identified. [7][8][9] Although mutations in the SIL1 gene account for the majority of MSS cases, Senderrek et al 5 reported four individuals with typical MSS lacking SIL1 mutations. These reports suggest genetic heterogeneity in MSS.…”

Section: Introductionmentioning

confidence: 99%

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Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco–Sjögren syndrome

Takahata

Yamada

et al. 2010

J Hum Genet

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Marinesco-Sjö gren syndrome (MSS) is a rare autosomal recessive disorder. Mutation in the SIL1 gene accounts for the majority of MSS cases. However, some individuals with typical MSS without SIL1 mutations have been reported. In this study, we identified two novel mutations in a Japanese pedigree with MSS, one of which was an intragenic deletion not detected using the PCR-direct sequencing protocol. This family consisted of three affected siblings, an unaffected sibling and unaffected parents. We found a homozygous 5-bp deletion, del598-602(GAAGA), in exon 6 of all affected siblings by PCR. Thus, we expected that both parents would be heterozygous for the mutation. As expected, the father was heterozygous, whereas the mother demonstrated no mutations. We then carried out array comparative genomic hybridization and quantitative PCR analyses, and identified an approximately 58 kb deletion in exon 6 in the patients and mother. As a result, the mother was hemizygous for a 58-kb deletion. The affected siblings contained two mutations, a 5-bp and a 58-kb deletion, resulting in SIL1 gene dysfunction. It is possible that some reported cases of MSS without base alterations in the SIL1 gene are caused by deletions rather than locus heterogeneity.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco–Sjögren syndrome

Takahata

Yamada

et al. 2010

J Hum Genet

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“…Additional reported eye findings include optic atrophy, glaucoma, microphthalmia, and retinal degeneration. 19 Congenital cataract-facial dysmorphism-neuropathy (CCFDN) syndrome is an autosomal recessive syndrome Figure 5 Dense nuclear sclerosis and posterior lenticonus in a CS2 patient. Congenital cataracts and microcephaly R Goyal et al described to date only in Vlax Roma gypsies.…”

Section: Discussionmentioning

confidence: 99%

Review of cases presenting with microcephaly and bilateral congenital cataract in a paediatric cataract clinic

Goyal

Thompson

Timms

et al. 2007

Eye

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Purpose We reviewed all children presenting with microcephaly and bilateral congenital cataract in our paediatric cataract clinic, to identify their underlying diagnosis and clinical features that could help in early diagnosis of such conditions. Methods We screened our cataract database to collect data on all children presenting to our institute with cataract before 1 year of age for a period of 5 years (1997)(1998)(1999)(2000)(2001) inclusive. We found 166 cases of cataract, of which 85 were bilateral. Of the 85 children with bilateral cataract, five also had microcephaly. The case notes of these five children were retrospectively reviewed for age at presentation, ocular and systemic examination findings, results of electro diagnostic testing, outcome of cataract surgery, and any additional investigation results. Results In our series, three children were diagnosed with early-onset Cockayne syndrome (CS2), one was diagnosed with Micro syndrome and one with HallermannStreiff syndrome. Electrodiagnostic testing was abnormal in four of the five cases, and growth failure was present in all five. There was a good outcome from surgery in the three children with CS2 and the child with Hallermann-Strieff. There was a poor outcome in the child with Micro syndrome. Conclusions The presence of microcephaly in children presenting with bilateral cataracts in infancy is strongly suggestive of a syndromic cause. Early-onset Cockayne syndrome was the commonest underlying diagnosis in our series, but clinicians should be aware of other possibilities, and we discuss the differential diagnosis. Head circumference should be checked routinely in children with congenital cataract.

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Redox Regulation of Protein Misfolding, Synaptic Damage, and Neuronal Loss in Neurodegenerative Diseases

Nakamura

Lipton

2011

Protein Chaperones and Protection From Neurodegenerative Diseases

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Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy

Cited by 230 publications

References 12 publications

Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco–Sjögren syndrome

Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco–Sjögren syndrome

Review of cases presenting with microcephaly and bilateral congenital cataract in a paediatric cataract clinic

Redox Regulation of Protein Misfolding, Synaptic Damage, and Neuronal Loss in Neurodegenerative Diseases

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