Mutations in MBOAT7 , Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features

Johansen, Anide; Rosti, Rasim Özgür; Musaev, Damir; Sticca, Evan; Harripaul, Ricardo; Zaki, Maha S.; Çağlayan, Ahmet Okay; Azam, Matloob; Sultan, Tipu; Froukh, Tawfiq; Reis, André; Popp, Bernt; Ahmed, Iltaf; John, Peter; Ayub, Muhammad; Ben‐Omran, Tawfeg; Vincent, John B.; Gleeson, Joseph G.; Jamra, Rami Abou

doi:10.1016/j.ajhg.2016.07.019

Cited by 76 publications

(86 citation statements)

References 33 publications

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“…Ataxic gait which could be accompanied by abnormal cerebellar tests was a universal finding in our patients. However, incoordination was not reported in the case series of Johansen et al Our patients were normocephalic documented in seven of 12 cases, similar to the patients reported by Johansen et al Similar facial features, strabismus and hypopigmented macules were additional clinical findings seen our patients which were not documented in the prior series …”

Section: Discussionsupporting

confidence: 87%

“…We present clinical and neuroimaging findings of 12 patients with MBOAT7 gene defect, which is the second series reported in literature. Johansen et al reported 16 patients with MBOAT7 gene defect from six families . In our series 12 patients come from seven families and parents are relatives in all patients compatible with autosomal recessive inheritance.…”

Section: Discussionmentioning

confidence: 71%

“…Until now no clinical phenotype neither human nor animal model have been reported related to 1‐acyl LPI acyl transferase deficiency coded by AGPAT8 gene. In 2016, Johansen et al reported MBOAT7 gene defect in 16 cases presenting with autistic findings, developmental delay, moderate to severe intellectual disability, epilepsy, nonverbal delayed milestones, truncal hypotonia, and appendicular hypertonia …”

Section: Introductionmentioning

confidence: 99%

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Expanding the phenotype of phospholipid remodelling disease due to MBOAT7 gene defect

Yalnızoğlu

Özgül

Oğuz

et al. 2019

J of Inher Metab Disea

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MBOAT7 gene codes O‐acyltransferase domain containing seven proteins which is one of four enzymes involved in remodeling of phosphoinositol phosphate (PIP) in LANDs cycle. We present clinical, neuroimaging, and genetic findings of 12 patients from 7 families with MBOAT7 gene defect, a recently defined novel phospholipid remodelling disease. To the best of our knowledge, our case series is the second report on patients with MBOAT7 gene defect. The patients present with global developmental delay particularly in speech and language skills, intellectual disability, stereotypical behavior, ataxic gait, early onset epilepsy with well response to medical treatment, strabismus and similar facial features. Common neuroimaging findings of the patients were folium dysgenesis of the cerebellum with a particular appearance, mild‐to‐moderate cerebellar atrophy, T2 hyperintensity of bilateral globus pallidius and dentate nuclei, enlarged perivascular areas, and mild thinning of the corpus callosum. Genome‐wide genotyping and exome sequencing identified five different types of homozygous mutations in the MBOAT7 gene in all seven families which are p.Arg87*, p.Leu227ProfsX65, p.Gln376Lys, p.Trp426*, and chr19:54.666.173‐54.677.766/11594 bp del. We conclude that clinical and neuroimaging findings of MBOAT7 gene defect may suggest the diagnosis and guide genetic tests.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expanding the phenotype of phospholipid remodelling disease due to MBOAT7 gene defect

Yalnızoğlu

Özgül

Oğuz

et al. 2019

J of Inher Metab Disea

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“…Unless indicated, these variants were absent in 194 unrelated Pakistani exomes with non-cognitive Mendelian phenotypes and in ~ 1000 unrelated individuals in the GME Variome Project. References per known gene: ALG3 (Riess et al 2013); ASPM (Kousar et al 2010); BCKDK (Novarino et al 2012); CRADD (Di Donato et al 2016; Harel et al 2017); CWF19L1 (Burns et al 2014; Nguyen et al 2016; Evers et al 2016); CYB5R3 (Ewenczyk et al 2008); GAN (Kuhlenbäumer et al 2002; Tazir et al 2009); LRP2 (Vasli et al 2016); MBOAT7 (Johansen et al 2016); MLYCD (Salomons et al 2007); PNKP (Shen et al 2010); SPTBN2 (Lise et al 2012); TUSC3 (Garshasbi et al 2008, 2011; Khan et al 2011; Loddo et al 2013; Al-Amri et al 2016); WDR62 (Wang et al 2017). …”

Section: Figmentioning

confidence: 99%

Novel candidate genes and variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability

Santos‐Cortez

Khan

et al. 2018

Hum Genet

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Identification of Mendelian genes for neurodevelopmental disorders using exome sequencing to study autosomal recessive (AR) consanguineous pedigrees has been highly successful. To identify causal variants for syndromic and non-syndromic intellectual disability (ID), exome sequencing was performed using DNA samples from 22 consanguineous Pakistani families with ARID, of which 21 have additional phenotypes including microcephaly. To aid in variant identification, homozygosity mapping and linkage analysis were performed. DNA samples from affected family member(s) from every pedigree underwent exome sequencing. Identified rare damaging exome variants were tested for co-segregation with ID using Sanger sequencing. For seven ARID families, variants were identified in genes not previously associated with ID, including: EI24, FXR1 and TET3 for which knockout mouse models have brain defects; and CACNG7 and TRAPPC10 where cell studies suggest roles in important neural pathways. For two families, the novel ARID genes CARNMT1 and GARNL3 lie within previously reported ID microdeletion regions. We also observed homozygous variants in two ID candidate genes, GRAMD1B and TBRG1, for which each has been previously reported in a single family. An additional 14 families have homozygous variants in established ID genes, of which 11 variants are novel. All ARID genes have increased expression in specific structures of the developing and adult human brain and 91% of the genes are differentially expressed in utero or during early childhood. The identification of novel ARID candidate genes and variants adds to the knowledge base that is required to further understand human brain function and development.

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“…Mutations responsible for ID were identified in three of the seven families, and several other candidates were also revealed. In addition, the genes DENND5A (DENN domain-containing protein 5A) and MBOAT7 (Lysophospholipid acyltransferase 7) were newly implicated in a distinctive subtype of epileptic encephalopathy and ID in studies of consanguineous families (Han et al 2016;Johansen et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Next Generation Sequencing and Genome-Wide Genotyping Identify the Genetic Causes of Intellectual Disability in Ten Consanguineous Families from Jordan

Froukh

2017

Tohoku J. Exp. Med.

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Intellectual disability (ID), occurs in approximately 1 to 3% of the population and tends to be higher in low-income countries and in inbred communities. Despite the high rates of consanguineous marriages and the likely enrichment for recessive forms of ID, the genetic bases of ID in Jordan are largely unstudied. In this study, whole exome sequencing (WES) and homozygosity mapping were used to identify the genetic causes of ID in ten families from Jordan. The studied families are characterized by consanguineous marriage and having one or more progeny with ID. Likely disease-causing missense mutations were identified in eight families; four families are due to mutations in genes previously implicated with ID and the other four families are due to mutations in genes that are not previously implicated with ID. The novel genes include: BSN (Protein Basson), PTCHD2 (Protein dispatched homolog 3), DHRS3 (Short-chain dehydrogenase/reductase 3), and LGI3 (Leucine-rich repeat LGI family member 3). In addition, copy number variant (CNV) deletion and/or duplication were identified in 2 families; one family with 3.5 mega base (Mb) deletion on chromosome17 previously implicated with Smith Magenis Syndrome, and the other family with a novel combination of deletion and duplication in chromosomes 5 and 11. In this pilot study, four genes and one CNV deletion/duplication are identified for the first time in association with ID. The finding of this study further demonstrates the power of WES and homozygosity mapping for clinical diagnostics of ID in consanguineous families in small populations.

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Mutations in MBOAT7 , Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features

Cited by 76 publications

References 33 publications

Expanding the phenotype of phospholipid remodelling disease due to MBOAT7 gene defect

Expanding the phenotype of phospholipid remodelling disease due to MBOAT7 gene defect

Novel candidate genes and variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability

Next Generation Sequencing and Genome-Wide Genotyping Identify the Genetic Causes of Intellectual Disability in Ten Consanguineous Families from Jordan

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