Mutations in ZBTB20 cause Primrose syndrome

Cordeddu, Viviana; Redeker, B.; Stellacci, Emilia; Jongejan, Aldo; Fragale, Alessandra; Bradley, Ted; Anselmi, Massimiliano; Ciolfi, Andrea; Cecchetti, Serena; Muto, Valentina; Bernardini, Laura; Azage, Meron; Carvalho, Daniel R.; Espay, Alberto J.; Male, Alison; Molin, Anna Maja; Posmyk, Renata; Battisti, Carla; Casertano, Alberto; Melis, Daniela; Kampen, Antoine van; Baas, Frank; Mannens, Marcel M.A.M.; Bocchinfuso, Gianfranco; Stella, Lorenzo; Tartaglia, Marco; Hennekam, Raoul C. M.

doi:10.1038/ng.3035

Cited by 80 publications

(116 citation statements)

References 36 publications

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“…org/gatk/guide/best-practices). Called variants were filtered as previously reported (Cordeddu et al 2014;Niceta et al 2015;Kortum et al 2015). The predicted functional effect of variants was annotated with SnpEff toolbox V.4.…”

Section: Whole Exome Sequencingmentioning

confidence: 99%

Expanding the molecular diversity and phenotypic spectrum of glycerol 3‐phosphate dehydrogenase 1 deficiency

Dionisi‐Vici

Shteyer

Niceta

et al. 2016

J of Inher Metab Disea

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Transient infantile hypertriglyceridemia (HTGT1; OMIM #614480) is a rare autosomal recessive disorder, which manifests in early infancy with transient hypertriglyceridemia, hepatomegaly, elevated liver enzymes, persistent fatty liver and hepatic fibrosis. This rare clinical entity is caused by inactivating mutations in the GPD1 gene, which encodes the cytosolic isoform of glycerol-3-phosphate dehydrogenase. Here we report on four patients from three unrelated families of diverse ethnic origins, who presented with hepatomegaly, liver steatosis, hypertriglyceridemia, with or without fasting ketotic hypoglycemia. Whole exome sequencing revealed the affected individuals to harbor deleterious biallelic mutations in the GPD1 gene, including the previously undescribed c.806G > A (p.Arg269Gln) and c.640T > C (p.Cys214Arg) mutations. The clinical features in three of our patients showed several differences compared to the original reports. One subject presented with recurrent episodes of fasting hypoglycemia along with hepatomegaly, hypetriglyceridemia, and elevated liver enzymes; the second showed a severe liver disease, with intrahepatic cholestasis associated with kidney involvement; finally, the third presented persistent hypertriglyceridemia at the age of 30 years. These findings expand the current knowledge of this rare disorder, both with regard to the phenotype and molecular basis. The enlarged phenotypic spectrum of glycerol-3-phosphate dehydrogenase 1 deficiency can mimic other inborn errors of metabolism with liver involvement and should alert clinicians to recognize this entity by considering GPD1 mutations in appropriate clinical settings.

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Section: Whole Exome Sequencingmentioning

confidence: 99%

Expanding the molecular diversity and phenotypic spectrum of glycerol 3‐phosphate dehydrogenase 1 deficiency

Dionisi‐Vici

Shteyer

Niceta

et al. 2016

J of Inher Metab Disea

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“…The mutation site of the ZBTB20 gene is conservative in all cases of Primrose syndrome, and the mutant amino acid residues are located in the first, second zinc finger region and the junction area of the zinc finger. In vitro experiments showed that the mutation of these loci reduced the binding ability of ZBTB20 protein to the target DNA fragments, and its ability of transcriptional inhibition was significantly reduced [17]. This finding establishes a genetic link between these disorders and delineates the impact of ZBTB20 dysregulation on brain development, cognitive function, growth and metabolism.…”

Section: Mental Illness With Znfsmentioning

confidence: 71%

“…ZBTB20 belongs to a family of transcription factors with an N-terminal BTB/POZ domain involved in protein-protein interaction and five C2H2 zinc fingers at the C terminus ( Figure 1), mediating protein binding to DNA [17]. ZBTB20 is expressed in developing neocortex and adult hippocampus.…”

Section: Mental Illness With Znfsmentioning

confidence: 99%

“…Whole-exome sequencing of 8 subjects with Primrose syndrome found missense mutations or microdeletion in ZBTB20 loci [17]. The mutation site of the ZBTB20 gene is conservative in all cases of Primrose syndrome, and the mutant amino acid residues are located in the first, second zinc finger region and the junction area of the zinc finger.…”

Section: Mental Illness With Znfsmentioning

confidence: 99%

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Zinc-Finger Proteins in Brain Development and Mental Illness

Li¹,

Lu²,

Liu³

2018

J Transl Neurosci

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Current genomic screening technologies race to screen genes involved in mental illness in large population or case by case patients including schizophrenia, bipolar disease, depression, autism spectrum disorders and intellectual disability. Among identified genes, zinc finger domain (ZNF/zfp) containing proteins come to attention. Copy number variant (CNV), single nucleotide polymorphism (SNP) as well as de novo mutations induced nonsense or missense mutations in proteins, have been found in a handful ZNF/zfp genes, much mutations are within or near zinc finger domains. Those genes are found to be expressed during early embryonic and postnatal development. Nevertheless, studies on roles of ZNF/zfp domain containing proteins and brain development are necessary to reveal pathogenesis of human mental illness. Here in this review, we summarize recent discoveries on mental illness related ZNF/zfp genes and their role in brain development.

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“…MRI may show basal ganglia calcifications. The condition is caused by ZBTB20 mutations [Cordeddu et al, 2014;Mattioli et al, 2016].…”

Section: Primrose Syndromementioning

confidence: 99%

A Clinical Review of Generalized Overgrowth Syndromes in the Era of Massively Parallel Sequencing

et al. 2018

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The overgrowth syndromes are important to diagnose, not just for accurate genetic counseling, but also for knowledge surrounding cancer surveillance and prognosis. There has been a recent expansion in the number of genes associated with a mendelian overgrowth phenotype, so this review updates previous classifications of overgrowth syndromes. We also describe a clinical and molecular approach to the investigation of individuals presenting with overgrowth. This review aims to assist the clinical diagnosis of generalized overgrowth syndromes by outlining the salient features of well-known overgrowth syndromes alongside the many syndromes that have been discovered and classified more recently. We provide key clinical “handles” to aid clinical diagnosis and a list of genes to aid with panel design when using next generation sequencing, which we believe is frequently needed due to the overlapping phenotypic features seen between overgrowth syndromes.

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Mutations in ZBTB20 cause Primrose syndrome

Cited by 80 publications

References 36 publications

Expanding the molecular diversity and phenotypic spectrum of glycerol 3‐phosphate dehydrogenase 1 deficiency

Expanding the molecular diversity and phenotypic spectrum of glycerol 3‐phosphate dehydrogenase 1 deficiency

Zinc-Finger Proteins in Brain Development and Mental Illness

A Clinical Review of Generalized Overgrowth Syndromes in the Era of Massively Parallel Sequencing

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