A Novel Mutation in the Sterol 27-hydroxylase Gene of a Pakistani Family with Autosomal Recessive Cerebrotendinous Xanthomatosis

AbstractAgenesis of the corpus callosum with peripheral neuropathy (ACCPN) or Andermann syndrome is an autosomal recessive condition caused by mutations in SLC12A6. The neurodegenerative features are characterized primarily by severe and progressive polyneuropathy, with eventual loss of ambulation and limited lifespan. We report two siblings with Andermann syndrome from a consanguineous Pakistani family with severe global developmental delays, sensory-motor polyneuropathy, and complete agenesis of the corpus callosum, associated with a homozygous c.745+2T>A mutation in SLC12A6. This sequence change is predicted to inactivate the donor splice site and abolish correct splicing of intron 6, yielding an abnormally truncated protein. This is the first report of Andermann syndrome in patients of Pakistani origin, which supports the pan-ethnic incidence of this condition.

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Mitochondrial Neurogastrointestinal Encephalomyopathy Disease in Three Siblings from Pakistan with a Novel Mutation

Journal of Pediatric Genetics ◽

10.1055/s-0038-1661411 ◽

2018 ◽

Vol 08 (01) ◽

pp. 015-019

Author(s):

Sana Durrani ◽

Bee Chen ◽

Yusnita Yakob ◽

Lua Hian ◽

Bushra Afroze

Keyword(s):

Thymidine Phosphorylase ◽

Autosomal Recessive ◽

Novel Mutation ◽

Gastrointestinal Symptoms ◽

Autosomal Recessive Disorder ◽

Homozygous Mutation ◽

Pakistani Family ◽

Mitochondrial Neurogastrointestinal Encephalomyopathy ◽

Intestinal Dysmotility ◽

Sensorineural Hearing Impairment

AbstractMitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare multisystem autosomal recessive disorder. The disease is clinically heterogeneous with gastrointestinal symptoms of intestinal dysmotility and cachexia as well as neurological symptoms of ophthalmoplegia, neuropathy, sensorineural hearing impairment, and diffuse leukoencephalopathy being most prominent. MNGIE is caused by mutations in TYMP, a gene that encodes thymidine phosphorylase (TP)—a cytosolic enzyme. Mutations in TYMP lead to very low TP catalytic activity, resulting in dramatically increased thymidine and deoxyuridine in plasma. We describe the clinical, biochemical, and neuroimaging findings of three boys with MNGIE from a Pakistani family with a novel homozygous mutation, c.798_801dupCGCG p. (Ala268Argfs*?), in exon 7 of TYMP.

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A novel mutation (86insA) in the alpha-sarcoglycan-gene leads to severe childhood autosomal recessive muscular dystrophy

Neuropediatrics ◽

10.1055/s-2004-819444 ◽

2004 ◽

Vol 35 (01) ◽

Author(s):

GP Ramelli ◽

F Joncourt ◽

M Gasparini ◽

P Tonin

Keyword(s):

Muscular Dystrophy ◽

Autosomal Recessive ◽

Novel Mutation

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Identification of new mutations in sterol 27-hydroxylase gene in Japanese patients with cerebrotendinous xanthomatosis (CTX).

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)40096-3 ◽

1994 ◽

Vol 35 (6) ◽

pp. 1031-1039

Author(s):

K S Kim ◽

S Kubota ◽

M Kuriyama ◽

J Fujiyama ◽

I Björkhem ◽

...

Keyword(s):

Japanese Patients ◽

Cerebrotendinous Xanthomatosis ◽

Hydroxylase Gene ◽

New Mutations

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Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis

Blood ◽

10.1182/blood.v100.2.692 ◽

2002 ◽

Vol 100 (2) ◽

pp. 692-694 ◽

Cited By ~ 113

Author(s):

Daniel F. Wallace ◽

Palle Pedersen ◽

Jeannette L. Dixon ◽

Peter Stephenson ◽

Jeffrey W. Searle ◽

...

Keyword(s):

Iron Transport ◽

Autosomal Recessive ◽

Iron Homeostasis ◽

Autosomal Dominant ◽

Novel Mutation ◽

Hfe Gene ◽

Excess Iron ◽

Chromosome 1Q ◽

Australian Family ◽

Autosomal Recessive Pattern

Abstract Hemochromatosis is a common disorder characterized by excess iron absorption and accumulation of iron in tissues. Usually hemochromatosis is inherited in an autosomal recessive pattern and is caused by mutations in the HFE gene. Less common non-HFE–related forms of hemochromatosis have been reported and are caused by mutations in the transferrin receptor 2 gene and in a gene localized to chromosome 1q. Autosomal dominant forms of hemochromatosis have also been described. Recently, 2 mutations in theferroportin1 gene, which encodes the iron transport protein ferroportin1, have been implicated in families with autosomal dominant hemochromatosis from the Netherlands and Italy. We report the finding of a novel mutation (V162del) in ferroportin1 in an Australian family with autosomal dominant hemochromatosis. We propose that this mutation disrupts the function of the ferroportin1 protein, leading to impaired iron homeostasis and iron overload.

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