The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy

We examined the deletion of the survival motor neuron [SMN] and neuronal apoptosis inhibitory protein [NAIP]genes in patients with spinal muscular atrophy [SMA] using polymerase chain reaction followed by restriction site assay methods. The study included 16 Saudi patients [9 SMA type I and 7 SMA type II]and 6 healthy Saudi volunteers. The homozygous deletions of exons 7 and 8 of the telomeric SMN gene, and exon 5 of the NAIP gene were found in all SMA type I patients. Exons 7 and 8 of telomeric SMN were deleted in all SMA type II patients. However, exon 5 of NAIP was deleted in three of the seven cases. All control volunteers and all family members of the patients had normal SMN and NAIP. The incidence of NAIP deletion was higher in the more severe SMA cases and the dual deletion of the SMN and NAIP genes was more common in Saudi SMA type I patients compared with patients of other ethnic groups

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Molecular Analysis of Survival Motor Neuron and Neuronal Apoptosis Inhibitory Protein Genes in Macedonian Spinal Muscular Atrophy Patients

Balkan Journal of Medical Genetics ◽

10.2478/v10034-008-0007-z ◽

2007 ◽

Vol 10 (2) ◽

pp. 55-60 ◽

Cited By ~ 1

Author(s):

S Kocheva ◽

S Vlaski-Jekic ◽

M Kuturec ◽

G Efremov

Keyword(s):

Motor Neuron ◽

Neuronal Apoptosis ◽

Muscular Atrophy ◽

Survival Motor Neuron ◽

Type I ◽

Type Ii ◽

Inhibitory Protein ◽

Neuronal Apoptosis Inhibitory Protein ◽

Smn Gene ◽

Naip Gene

Molecular Analysis of Survival Motor Neuron and Neuronal Apoptosis Inhibitory Protein Genes in Macedonian Spinal Muscular Atrophy PatientsSpinal muscular atrophy (SMA) is classified according to the age of onset and severity of the clinical manifestations into: acute (Werding-Hoffman disease or type I), intermediate (type II) and juvenile (Kugelberg-Wilander disease or type III) forms. All three SMAs have been linked to markers at 5q11.2-q13.3. Two candidate genes deleted in SMA patients are the survival motor neuron (SMN) gene and the neuronal apoptosis inhibitory protein (NAIP) gene. We have performed molecular analyses of these genes in 30 unrelated Macedonian families (17 with type I, eight with type II and five with type III forms of the disease). Deletions of exons 7 and 8 of the SMN gene were found in 76.6% (23/30) of patients (94.1% in type I, 87.5% in type II). Among these 23 families, 19 had both exons deleted, while four had deletions only of exon 7. Deletions of exon 5 of the NAIP gene were found in 41.2% (7/17) patients with type I SMA and in 12.5% (1/8) of patients with type II SMA. No deletions of the SMN gene were found in 30 parents and 30 normal controls. We found 2/30 (6.7%) parents to be homozygous for the deletion of exon 5. Our data support the hypothesis that the telomeric SMN gene plays a major role in determining the clinical course of the disease, while the defects in the NAIP gene have only a modifying effect on the phenotype.

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Distribution of Neuronal Apoptosis Inhibitory Protein in Human Tissues

Journal of Histochemistry & Cytochemistry ◽

10.1369/jhc.6a7144.2007 ◽

2007 ◽

Vol 55 (9) ◽

pp. 911-923 ◽

Cited By ~ 22

Author(s):

Johannes K. X. Maier ◽

Sylvia Balabanian ◽

Cynthia R. Coffill ◽

Alexandra Stewart ◽

Louise Pelletier ◽

...

Keyword(s):

Western Blot ◽

Neuronal Apoptosis ◽

Muscular Atrophy ◽

Detection Methods ◽

Inhibitory Protein ◽

Neuronal Apoptosis Inhibitory Protein ◽

Recognition Protein ◽

Intestinal Pathogen ◽

The Central Nervous System ◽

Naip Gene

The neuronal apoptosis inhibitory protein (NAIP) gene, also known as the baculovirus inhibitor of apoptosis repeat-containing protein 1 (BIRC1) gene, is a member of the inhibitors of apoptosis (IAP) family and was first characterized as a candidate gene for spinal muscular atrophy (SMA). The expression of NAIP has been thoroughly studied in the central nervous system and overlaps the pattern of neurodegeneration in SMA. Recent studies have pointed to a role for NAIP in non-neuronal cells. We report here the production of a specific anti-NAIP antibody and the profile of NAIP expression in human adult tissues by Western blot and immunohistochemical detection methods. NAIP was detected in a number of tissues by Western blot analysis, but immunohistochemistry revealed that NAIP's presence in certain tissues, such as liver, lung, and spleen, is most likely due to macrophage infiltration. In the small intestine, the expression of NAIP coincides with the expression of p21WAF1. This observation, coupled with findings from other groups, suggests a role for NAIP in increasing the survival of cells undergoing terminal differentiation as well as the possibility that the protein serves as an intestinal pathogen recognition protein. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.

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