Spinal Müsküler Atrofi ve Moleküler Genetiği
Spinal Muscular Atrophy and Its Molecular Genetics
Yazar: Sel, Sabriye Kocatürk; Kasap, Halil; Koç, Filiz; Güzel, Ali İrfan
Dergi: Arşiv Kaynak Tarama Dergisi, Vol. 21 No. 1, 2014
Anahtar kelimeler: HDAC inhibitors,  SMA , SMN1, SMN2 ; HDAC inhibitörleri, SMA, SMN1, SMN2

Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases, affecting aproximately 1 in 6,000 - 10,000 live births, and with a carrier frequency of aproximately 1 in 40- 60. The childhood SMAs can be classified clinically into three groups. Type I (Werdnig-Hoffmann) is the most severe form, with onset at &#8249; 6 months of age and with death typically at &#8249;2 years of age. Type II SMA patients display an intermediate severity, with onset at &#8249;18 months of age and with an inability to walk. Type III (Kugelberg &#8211;Walender) individuals are able to walk independently and have a relatively mild phenotype, with onset at &#8250;18 months of age. The gene involved in type I&#8211;III SMA has been mapped to 5q12-q13 by linkage analysis, and refined to a region of about 500 kb. The region contains a large inverted duplication consisting of at least four genes, which are present in a telomeric (t) and a centromeric (c) copy: survival motor neuron gene (SMN1 or SMNt and SMN2 or SMNc); neuronal apoptosis inhibitory protein gene (NAIP); basal transcription factor subunit p44 (BTFp44t and BTFp44c); and a novel protein with unknown function H4F5.  Although homozygous deletions encompassing all these genes are found in SMA patients, it is now well established that mutations or deletions of SMN1 (MIM#600354) cause the disease. SMN2 (MIM# 601627) gene, however, does not prevent the disease but attenuates disease severity. Therefore, upregulating functional SMN protein level via inducing gene expression and/or restoring splicing is an important therapeutic approach such as use of histone deacetylase (HDAC) inhibitors.

Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases, affecting aproximately 1 in 6,000 - 10,000 live births, and with a carrier frequency of aproximately 1 in 40- 60. The childhood SMAs can be classified clinically into three groups. Type I (Werdnig-Hoffmann) is the most severe form, with onset at &#8249; 6 months of age and with death typically at &#8249;2 years of age. Type II SMA patients display an intermediate severity, with onset at &#8249;18 months of age and with an inability to walk. Type III (Kugelberg &#8211;Walender) individuals are able to walk independently and have a relatively mild phenotype, with onset at &#8250;18 months of age. The gene involved in type I&#8211;III SMA has been mapped to 5q12-q13 by linkage analysis, and refined to a region of about 500 kb. The region contains a large inverted duplication consisting of at least four genes, which are present in a telomeric (t) and a centromeric (c) copy: survival motor neuron gene (SMN1 or SMNt and SMN2 or SMNc); neuronal apoptosis inhibitory protein gene (NAIP); basal transcription factor subunit p44 (BTFp44t and BTFp44c); and a novel protein with unknown function H4F5.  Although homozygous deletions encompassing all these genes are found in SMA patients, it is now well established that mutations or deletions of SMN1 (MIM#600354) cause the disease. SMN2 (MIM# 601627) gene, however, does not prevent the disease but attenuates disease severity. Therefore, upregulating functional SMN protein level via inducing gene expression and/or restoring splicing is an important therapeutic approach such as use of histone deacetylase (HDAC) inhibitors.