Correlation of SMN2, NAIP, p44, H4F5 and Occludin genes copy number with spinal muscular atrophy phenotype in Tunisian patients

Amara, Abdelbasset; Adala, Labiba; Charfeddine, Ilhem Ben; Mamaï, Ons; Mili, Ali; Lazreg, Taheni Ben; Hmida, D.; Amri, F.; Salem, N.; Boughammura, Lamia; Saâd, Ali; Gribaa, Moez

doi:10.1016/j.ejpn.2011.07.007

Cited by 41 publications

(30 citation statements)

References 23 publications

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“…Similarly, other groups reported that NAIP homozygous deletion occurred more frequently in severe Type I SMA (40-80 %) compared to the milder Types II, III, and IV (\30 %) [16][17][18][19][20][21][22]. Furthermore, the frequency of this deletion varies between ethnicities; with the highest found in Tunisia, Iran and Turkey (88, 87 and 75 %, respectively) and the lowest in Bulgaria, Serbia and Croatia (26, 20 and 15 %, respectively) [17,19,21,[23][24][25]. The Cypriot frequency of 86 % lies amongst the highest and is similar to populations like Turkey and Tunisia which are of close geographical proximity.…”

Section: Discussionmentioning

confidence: 89%

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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Section: Discussionmentioning

confidence: 89%

Genetic findings of Cypriot spinal muscular atrophy patients

et al. 2015

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“…We performed a real‐time SYBR Green I dye–based qPCR assay using primers15 to quantify the copy numbers of SMN1 exon 7, SMN2 exon 7, and the SMN1 ‐neighboring genes NAIP (neuronal apoptosis inhibitory protein) exon 5 and H4F5t exon 2 in 200 Malian DNA samples. Three Tunisian DNA samples with known copy number were used as controls 15.…”

Section: Methodsmentioning

confidence: 99%

“…Three Tunisian DNA samples with known copy number were used as controls 15. We compared the copy numbers of SMN1 exon 7 and the other genes to assess duplication at the SMA locus, using the Pearson chi‐square test and p < 0.05 to indicate a significant difference.…”

Section: Methodsmentioning

confidence: 99%

Genetics of low spinal muscular atrophy carrier frequency in sub‐Saharan Africa

Sangaré

Hendrickson

Sango

et al. 2014

Annals of Neurology

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ObjectiveSpinal muscular atrophy (SMA) is one of the most common severe hereditary diseases of infancy and early childhood in North America, Europe, and Asia. SMA is usually caused by deletions of the survival motor neuron 1 (SMN1) gene. A closely related gene, SMN2, modifies the disease severity. SMA carriers have only 1 copy of SMN1 and are relatively common (1 in 30–50) in populations of European and Asian descent. SMN copy numbers and SMA carrier frequencies have not been reliably estimated in Malians and other sub‐Saharan Africans.MethodsWe used a quantitative polymerase chain reaction assay to determine SMN1 and SMN2 copy numbers in 628 Malians, 120 Nigerians, and 120 Kenyans. We also explored possible mechanisms for SMN1 and SMN2 copy number differences in Malians, and investigated their effects on SMN mRNA and protein levels.ResultsThe SMA carrier frequency in Malians is 1 in 209, lower than in Eurasians. Malians and other sub‐Saharan Africans are more likely to have ≥3 copies of SMN1 than Eurasians, and more likely to lack SMN2 than Europeans. There was no evidence of gene conversion, gene locus duplication, or natural selection from malaria resistance to account for the higher SMN1 copy numbers in Malians. High SMN1 copy numbers were not associated with increased SMN mRNA or protein levels in human cell lines.InterpretationSMA carrier frequencies are much lower in sub‐Saharan Africans than in Eurasians. This finding is important to consider in SMA genetic counseling in individuals with black African ancestry. Ann Neurol 2014;75:525–532

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“…29 Since this first report, this simple, rapid and reproducible method has been used in diagnostic laboratories to detect rearrangements in numerous genes such as CFTR 30 or SMN1. 31 Herein, we designed a QMPSF strategy to identify POLG large-scale rearrangements. Among the seven patients with only one identified mutant POLG allele, we identified a large intragenic deletion in a young child carrying a single heterozygous p.Trp748Ser mutation.…”

Section: Discussionmentioning

confidence: 99%

Quantitative multiplex PCR of short fluorescent fragments for the detection of large intragenic POLG rearrangements in a large French cohort

et al. 2013

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Polymerase gamma (POLG) is the gene most commonly involved in mitochondrial disorders with mitochondrial DNA instability and causes a wide range of diseases with recessive or dominant transmission. More than 170 mutations have been reported. Most of them are missense mutations, although nonsense mutations, splice-site mutations, small deletions and insertions have also been identified. However, to date, only one large-scale rearrangement has been described in a child with Alpers syndrome. Below, we report a large cohort of 160 patients with clinical, molecular and/or biochemical presentation suggestive of POLG deficiency. Using sequencing, we identified POLG variants in 22 patients (18 kindreds) including five novel pathogenic mutations. Two patients with novel mutations had unusual clinical presentation: the first exhibited an isolated ataxic neuropathy and the second was a child who presented with endocrine signs. We completed the sequencing step by quantitative multiplex PCR of short fluorescent fragments (QMPSF) analysis in 37 patients with either only one POLG heterozygous variant or a family history suggesting a dominant transmission. We identified a large intragenic deletion encompassing part of intron 21 and exon 22 of POLG in a child with refractory epilepsia partialis continua. In conclusion, we describe the first large French cohort of patients with POLG mutations, expanding the wide clinical and molecular spectrum observed in POLG disease. We confirm that large deletions in the POLG gene are rare events and we highlight the importance of QMPSF in patients with a single heterozygous POLG mutation, particularly in severe infantile phenotypes.

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Correlation of SMN2, NAIP, p44, H4F5 and Occludin genes copy number with spinal muscular atrophy phenotype in Tunisian patients

Cited by 41 publications

References 23 publications

Genetic findings of Cypriot spinal muscular atrophy patients

Genetic findings of Cypriot spinal muscular atrophy patients

Genetics of low spinal muscular atrophy carrier frequency in sub‐Saharan Africa

Quantitative multiplex PCR of short fluorescent fragments for the detection of large intragenic POLG rearrangements in a large French cohort

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