A novel <i>ALDH5A1</i> mutation is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family

Püttmann, Lucia; Stehr, Henning; Garshasbi, Masoud; Hu, Hao; Kahrizi, Kimia; Lipkowitz, Bettina; Jamali, Payman; Tzschach, Andreas; Najmabadi, Hossein; Ropers, Hans‐Hilger; Musante, Luciana; Kuß, Andreas W.

doi:10.1002/ajmg.a.36030

Cited by 18 publications

(13 citation statements)

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“…Case ascertainment dating back to the initial report of gamma-hydroxybutyric aciduria identified 91 unique patients with clinical details provided (Aoshima et al 2002;Bekri et al 2004;Brown et al 1987;Dayan et al 2006;Deng et al 2011;Divry et al 1983;Escalera et al 2010;Gogou et al 2016;Haan et al 1985; Ishiguro et al 2001; Jakobs et al 1981;Jiang et al 2013;Kratz 2009;Kwok et al 2012;Lemes et al 2006;Li et al 2015;Lin et al 2015;Liu et al 2016;Neu et al 2002;Niemi et al 2014;O'Rourke et al 2010;Onkenhout et al 1989;Pearl et al 2003;Peters et al 1999;Puttmann et al 2013;Racaru et al 2010;Rashed et al 1994;Rating et al 1984;Saronwala et al 2008;Spilioti et al 2013;Tay et al 2015;Wang et al 2016;Yamakawa et al 2012;Zhao et al 2003;Ziyeh et al 2002). We furthermore identified 91 additional subjects with confirmed SSADH deficiency in our database published in aggregate (Parviz et al 2014).…”

Section: Case Reports and Resultsmentioning

confidence: 99%

Incidence and Geographic Distribution of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency

et al. 2016

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The incidence of succinic semialdehyde dehydrogenase (SSADH) deficiency, an autosomal recessive inherited disorder of GABA degradation, is unknown. Upon a recent diagnosis of a new family of affected fraternal twins from the Punjabi ethnic group of India, case ascertainment from the literature and our database was done to determine the number of confirmed cases along with their geographic distribution. The probands presented with global developmental delay, infantile onset epilepsy, and a persistent neurodevelopmental disorder upon diagnosis at 10 years of age with intellectual disability, expressive aphasia, and behavioral problems most prominent for hyperactivity. Gamma-hydroxybutyric aciduria and homozygous ALDH5A1 c.608C>T; p.Pro203Leu mutations were confirmed. Identification of all available individual cases with clinical details available including geographic or ethnic origin revealed 182 patients from 40 countries, with the largest number of patients reported from the USA (24%), Turkey (10%), China (7%), Saudi Arabia (6%), and Germany (5%). This study provides an accounting of all published cases of confirmed SSADH deficiency and provides data useful in planning further studies of this rare inborn error of metabolism.

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Section: Case Reports and Resultsmentioning

confidence: 99%

Incidence and Geographic Distribution of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency

et al. 2016

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“…Alterations of several well-conserved glycine residues, previously reported as critical for enzyme function in the aldehyde dehydrogenase superfamily, led to nearly complete ablation of enzyme activity (Akaboshi et al 2003). Since the report by Akaboshi and colleagues, only sporadic reports of inherited mutations have been presented (Lin et al 2015; Tay et al 2015; Jiang et al 2013; Puttman et al 2013; Kwok et al 2012; Lemes et al 2006; Bekri et al 2004). Many of these alleles are predicted to be pathogenic using SIFT analysis, but a comprehensive analysis of mutations has yet to be presented since that of Akaboshi in 2003.…”

Section: Molecular Genetics Of the Aldh5a1 Gene Encoding Ssadhmentioning

confidence: 99%

Succinic semialdehyde dehydrogenase deficiency (SSADHD): Pathophysiological complexity and multifactorial trait associations in a rare monogenic disorder of GABA metabolism

Malaspina

Roullet

Pearl

et al. 2016

Neurochemistry International

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Discovered some 35 years ago, succinic semialdehyde dehydrogenase deficiency (SSADHD) represents a rare, autosomal recessively-inherited defect in the second step of the GABA degradative pathway. Some 200 patients have been reported, with broad phenotypic and genotypic heterogeneity. SSADHD represents an unusual neurometabolic disorder in which two neuromodulatory agents, GABA (and the GABA analogue, 4-hydroxybutyrate), accumulate to supraphysiological levels. The unexpected occurrence of epilepsy in several patients is counterintuitive in view of the hyperGABAergic state, in which sedation might be expected. However, the epileptic status of some patients is most likely represented by broader imbalances of GABAergic and glutamatergic neurotransmission. Cumulative research encompassing decades of basic and clinical study of SSADHD reveal a monogenic disease with broad pathophysiological and clinical phenotypes. Numerous metabolic perturbations unmasked in SSADHD include alterations in oxidative stress parameters, dysregulation of autophagy and mitophagy, dysregulation of both inhibitory and excitatory neurotransmitters and gene expression, and unique subsets of SNP alterations of the SSADH gene (so-called ALDH5A1, or aldehyde dehydrogenase 5A1 gene) on the 6p22 chromosomal arm. While seemingly difficult to collate and interpret, these anomalies have continued to open novel pathways for pharmacotherapeutic considerations. Here, we present an update on selected aspects of SSADHD, the ALDH5A1 gene, and future avenues for research on this rare disorder of GABA metabolism.

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“…It is a key enzyme in the catabolism of gamma‐aminobutyric acid (GABA), and it plays a major role in anticonvulsant activity (Kumar, Kumar, & Punekar, ; Piplani, Verma, & Kumar, ). Deficiency of SSD may lead to neurologic disorders (Gahr, Connemann, Schönfeldt‐Lecuona, & Freudenmann, ; Lin, Weng, & Lee, ; Püttmann et al., ). Currently, researchers are focusing on the structure and dynamics of SSD (Jang, Park, Chi, & Lee, ; Park, Park, & Lee, ); however, there is limited information on its expression and variations in organisms.…”

Section: Discussionmentioning

confidence: 99%

“…It is a key enzyme in the catabolism of gamma-aminobutyric acid (GABA), and it plays a major role in anticonvulsant activity (Kumar, Kumar, & Punekar, 2015;Piplani, Verma, & Kumar, 2016). Deficiency of SSD may lead to neurologic disorders (Gahr, Connemann, Schönfeldt-Lecuona, & Freudenmann, 2013;Lin, Weng, & Lee, 2015;Püttmann et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Identification of suitable reference genes during the formation of chlamydospores in Clonostachys rosea 67‐1

Zhang

Sun

et al. 2017

MicrobiologyOpen

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Clonostachys rosea is a potential biocontrol fungus that can produce highly resistant chlamydospores under specific conditions. To investigate the genes related to chlamydospore formation, we identified reliable reference genes for quantification of gene expression in C. rosea 67‐1 during sporulation. In this study, nine reference genes, actin (ACT), elongation factor 1 (EF1), glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), histone (HIS), RNA polymerase II CTD phosphatase Fcp1 (RPP), succinate‐semialdehyde dehydrogenase (SSD), TATA‐binding protein (TBP), ubiquitin (UBQ), and ubiquitin‐conjugating enzyme (UCE), were selected and cloned from 67‐1, and their expression stability during chlamydospore formation was determined using reverse transcription quantitative PCR and assessed using the software geNorm, NormFinder and BestKeeper. The Ct values of the candidates ranged from 19.9 to 29.7, among which HIS,ACT and SSD exhibited high expression levels. The statistical analysis showed that ACT and SSD were most stably expressed, while UBQ and GAPDH showed relatively large variations under different culture conditions. Calculation of pairwise variation value indicated that two reference genes were required for precise quantification. Finally, ACT and SSD were selected to normalize gene expression during chlamydospore production in C. rosea 67‐1. To the best of our knowledge, this is the first report of SSD as a reference gene. This study will facilitate the accurate quantification of differentially expressed genes during the generation of chlamydospores and contribute to the investigation of the molecular mechanism underlying chlamydospore formation in C. rosea.

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A novel ALDH5A1 mutation is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family

Cited by 18 publications

References 50 publications

Incidence and Geographic Distribution of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency

Incidence and Geographic Distribution of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency

Succinic semialdehyde dehydrogenase deficiency (SSADHD): Pathophysiological complexity and multifactorial trait associations in a rare monogenic disorder of GABA metabolism

Identification of suitable reference genes during the formation of chlamydospores in Clonostachys rosea 67‐1

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