Molecular Analysis of the SMN1 and NAIP Genes in Iranian Patients with Spinal Muscular Atrophy

Derakhshandeh-Peykar, Pupak; Esmaili, Mohsen; Ousati-Ashtiani, Zahra; Rahmani, Mohammad; Babrzadeh, Farbod; Farshidi, Shahla; Attaran, Elham; Sajedifar, Mohammad Mehdi; Farhud, Dariush D.

doi:10.47102/annals-acadmedsg.v36n11p937

Cited by 9 publications

(1 citation statement)

References 29 publications

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“…The rate of consanguineous marriages in our study was 23.5%; an SMA study from Iran reported 97% consanguinity, 24 68% consanguinity was reported in a study from Turkey, 18 a prenatal diagnosis study from Turkey reported consanguinity in 21 of 63 families 25 because autosomal recessive diseases are a common result of consanguinity. The rate of consanguinity in our study is at a lower rate for our country.…”

Section: Discussionsupporting

confidence: 41%

The Frequency of SMN1, SMN2 Copy Numbers in 246 Turkish Cases Analyzed with MLPA Method

et al. 2023

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This study aimed to define the copy numbers of SMN1 and SMN2 genes and the diagnosis rate and carrier frequency of spinal muscular atrophy (SMA) in the Thrace region of Turkey. In this study, the frequency of deletions in exons 7 and 8 in the SMN1 gene and SMN2 copy numbers were investigated. A total of 133 cases with the preliminary diagnosis of SMA and 113 cases with the suspicion of being an SMA carrier from independent families were analyzed by multiplex ligation-dependent probe amplification method for SMN1 and SMN2 gene copy numbers. SMN1 homozygous deletions were detected in 34 patients (25.5%) of 133 cases with the suspicion of SMA. Cases diagnosed with SMA type I was 41.17% (14/34), 29.4% (10/34) with type II, 26.4% (9/34) with type III, and 2.94% (1/34) with type IV. The SMA carrier rate was 46.01% in 113 cases. In 34 SMA cases, SMN2 copy numbers were: two copies – 28 cases (82.3%), three copies – 6 cases (17.6%). SMN2 homozygous deletions were detected in 15% (17/113) of carrier analysis cases. The consanguinity rate of the parents was 23.5% in SMA diagnosed cases. In this study, we had a 25.5% of SMA diagnosis rate and 46% SMA carrier frequency. The current study also showed the relatively low consanguinity rate of the Thrace region, with 23.5% according to the east of Turkey.

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Section: Discussionsupporting

confidence: 41%

The Frequency of SMN1, SMN2 Copy Numbers in 246 Turkish Cases Analyzed with MLPA Method

et al. 2023

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Genetic findings of Cypriot spinal muscular atrophy patients

et al. 2015

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Spinal muscular atrophy (SMA) is an autosomal recessive, neurodegenerative disorder characterised commonly by proximal muscle weakness and wasting in the absence of sensory signs. Deletion or disruption of the SMN1 gene causes the disease. The SMN1 gene is located within an inverted duplication on chromosome 5q13 with the genes SMN2, NAIP and GTF2H2. MLPA analysis of 13 Cypriot SMA patients revealed that, 12 patients carried a homozygous SMN1 gene deletion and one patient carried two copies of the SMN1 gene. Two of 13 cases were a consequence of a paternally originating de novo mutation. Five genotypes were identified within the population, with the most frequent being a homozygous SMN1 and NAIP genes deletion. In conclusion, genotype-phenotype correlation revealed that SMN2 is inversely related to disease severity and that NAIP and GTF2H2 act as negative modifiers. This study provided, for the first time, a comprehensive overview of gene copy numbers and inheritance patterns within Cypriot SMA families.

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Evaluation of theSMNandNAIPGenes in a Family: Homozygous Deletion of theSMN2Gene in the Fetus and Outcome of the Pregnancy

Çoğulu

Durmaz

Pehlıvan

et al. 2009

Genetic Testing and Molecular Biomarkers

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S pinal muscular atrophy (SMA) is characterized by the death of motor neurons that leads to diffuse proximal and distal weakness, hypotonia, and muscular atrophy. Survival motor neuron (SMN), neuronal apoptosis inhibitory protein (NAIP), and GTF2H2 genes were shown to be associated with SMA. SMN protein is encoded by two genes that are two almost identical copies, telomeric SMN (SMN1) and centromeric SMN (SMN2). The SMN1 gene is homozygously absent in approximately 95% of SMA patients, whereas loss of SMN2 has been reported not to cause SMA. Prenatal diagnosis is widely applied for those pregnancies at risk for SMA, and here we present a family in which each of the parents is carrying SMN1 and NAIP gene deletions in one allele and SMN2 deletion in the other. Their first child was carrying SMN1 and NAIP gene deletions in both alleles and died at the age of 9 months. During the second pregnancy, the fetus was found to carry SMN2 deletion in both alleles, and the pregnancy was not terminated.The family was referred to our genetics department because of a risk of spinal muscular atrophy (SMA) in the fetus. The previous child of the family was found to have SMA and died at the age of 9 months. He was noted to have generalized weakness and severe hypotonia, absent stretched reflexes, and fasciculation in the tongue at the age of 4 months. The serum creatine kinase level was 28 IU. The electromyelography showed denervation of the muscles, paucity of movement, and fasciculation. The muscle biopsy revealed degeneration of muscle fibers without inflammation, fibrosis, or histochemical abnormality. Restriction fragment length polymorphism (RFLP) method was used for detecting the deletion within the survival motor neuron (SMN) gene. For exon 7 deletion and exon 8 deletion, restriction enzymes DraI and DdeI were used, respectively. DNA analysis revealed exon 7 and exon 8 deletions of the SMN gene and exon 6 of the NAIP gene on both chromosomes 5. The parents were considered to carry centromeric SMN (cenSMN-SMN2) deletion in one allele, and telomeric SMN (telSMN-SMN1) and NAIP gene deletions in the other allele. During the second pregnancy, chorionic villus sampling was performed at 11 weeks of gestation, and DNA was extracted to screen for SMA-causing mutations. The results showed deletions of exons 7 and 8 of the SMN2 gene on both chromosomes 5, while no deletion was detected in the SMN1 gene. The pregnancy was not terminated according to the mutation analysis, and the mother gave birth to a healthy male child. Clinical assessments during the growing-up period and the physical examination of the child at the age of 4 years were normal.Homozygous deletion of the SMN2 gene is presented in this report. SMA is caused by mutations in the telomeric SMN1 gene. Deletions in exons 7 and 8 of the telomeric copy occur in more than 90% of patients regardless of the disease severity (Lefebvre et al., 1995). It has been suggested that SMN2 copy number modulates the severity of the disease (MacLeod et al., 1999). Homozygous deletion of exo...

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Molecular Analysis of the SMN1 and NAIP Genes in Iranian Patients with Spinal Muscular Atrophy

Cited by 9 publications

References 29 publications

The Frequency of SMN1, SMN2 Copy Numbers in 246 Turkish Cases Analyzed with MLPA Method

The Frequency of SMN1, SMN2 Copy Numbers in 246 Turkish Cases Analyzed with MLPA Method

Genetic findings of Cypriot spinal muscular atrophy patients

Evaluation of theSMNandNAIPGenes in a Family: Homozygous Deletion of theSMN2Gene in the Fetus and Outcome of the Pregnancy

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