Publications by authors named "Sylvie Picker-Minh"

8 Publications

  • Page 1 of 1

Identification of a novel homozygous TRAPPC9 gene mutation causing non-syndromic intellectual disability, speech disorder, and secondary microcephaly.

Am J Med Genet B Neuropsychiatr Genet 2017 Dec 14;174(8):839-845. Epub 2017 Oct 14.

Charité - Universitätsmedizin Berlin, Institute of Neuroanatomy and Cell Biology, Berlin, Germany.

TRAPPC9 gene mutations have been linked recently to autosomal recessive mental retardation 13 (MRT13; MIM#613192) with only eight families reported world-wide. We assessed patients from two consanguineous pedigrees of Pakistani descent with non-syndromic intellectual disability and postnatal microcephaly through whole exome sequencing (WES) and cosegregation analysis. Here we report six further patients from two pedigrees with homozygous TRAPPC9 gene mutations, the novel nonsense mutation c.2065G>T (p.E689*) and the previously identified nonsense mutation c.1423C>T (p.R475*). We provide an overview of previously reported clinical features and highlight common symptoms and variability of MRT13. Common findings are intellectual disability and absent speech, and frequently microcephaly, motor delay and pathological findings on MRI including diminished cerebral white matter volume are present. Mutations in TRAPPC9 should be considered in non-syndromic autosomal recessive intellectual disability with severe speech disorder.
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http://dx.doi.org/10.1002/ajmg.b.32602DOI Listing
December 2017

Recessive mutation in EXOSC3 associates with mitochondrial dysfunction and pontocerebellar hypoplasia.

Mitochondrion 2017 11 4;37:46-54. Epub 2017 Jul 4.

NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; Department of Neuropediatrics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany. Electronic address:

Recessive mutations in EXOSC3, encoding a subunit of the human RNA exosome complex, cause pontocerebellar hypoplasia type 1b (PCH1B). We report a boy with severe muscular hypotonia, psychomotor retardation, progressive microcephaly, and cerebellar atrophy. Biochemical abnormalities comprised mitochondrial complex I and pyruvate dehydrogenase complex (PDHc) deficiency. Whole exome sequencing uncovered a known EXOSC3 mutation p.(D132A) as the underlying cause. In patient fibroblasts, a large portion of the EXOSC3 protein was trapped in the cytosol. MtDNA copy numbers in muscle were reduced to 35%, but mutations in the mtDNA and in nuclear mitochondrial genes were ruled out. RNA-Seq of patient muscle showed highly increased mRNA copy numbers, especially for genes encoding structural subunits of OXPHOS complexes I, III, and IV, possibly due to reduced degradation by a dysfunctional exosome complex. This is the first case of mitochondrial dysfunction associated with an EXOSC3 mutation, which expands the phenotypic spectrum of PCH1B. We discuss the links between exosome and mitochondrial dysfunction.
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http://dx.doi.org/10.1016/j.mito.2017.06.007DOI Listing
November 2017

Pontine Tegmental Cap Dysplasia in an Extremely Preterm Infant and Review of the Literature.

J Child Neurol 2017 03 20;32(3):334-340. Epub 2016 Dec 20.

2 Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Pontine tegmental cap dysplasia is a rare hindbrain malformation syndrome with a hypoplastic pons, a tissue protrusion into the fourth ventricle, and cranial nerve dysfunction. We here report clinical, imaging, and genetic findings of the first extremely low-birth-weight preterm infant with pontine tegmental cap dysplasia born at 25 weeks of gestation and provide an overview of 29 sporadic cases. A prenatally diagnosed hypoplastic and rostrally shifted cerebellum was indicative of a hindbrain defect and later identified as an early sign of pontine tegmental cap dysplasia in our patient. The neonate exhibited severe muscle hypotonia, persistent thermolability, and clinical signs of an involvement of facial, cochlear, and hypoglossal nerves. Furthermore, paroxysmal episodes of agonizing pain with facial tics, tonic and clonic muscle contractions, blepharospasm, and singultus are highlighted as new phenotypic features of pontine tegmental cap dysplasia. With our report, we present a severe case of pontine tegmental cap dysplasia and provide a brief overview of current knowledge on this rare disease.
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http://dx.doi.org/10.1177/0883073816680748DOI Listing
March 2017

Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD.

Orphanet J Rare Dis 2016 04 29;11(1):52. Epub 2016 Apr 29.

Department of Pediatric Neurology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.

Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity.
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http://dx.doi.org/10.1186/s13023-016-0433-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850685PMC
April 2016

Genetic causes of MCPH in consanguineous Pakistani families.

Clin Genet 2016 06 8;89(6):744-5. Epub 2015 Nov 8.

Institute of Cell Biology and Neurobiology, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan.

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http://dx.doi.org/10.1111/cge.12685DOI Listing
June 2016

Redefining the MED13L syndrome.

Eur J Hum Genet 2015 Oct 11;23(10):1308-17. Epub 2015 Mar 11.

Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits.
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http://dx.doi.org/10.1038/ejhg.2015.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592099PMC
October 2015

Large homozygous RAB3GAP1 gene microdeletion causes Warburg micro syndrome 1.

Orphanet J Rare Dis 2014 Oct 21;9:113. Epub 2014 Oct 21.

Warburg micro syndrome (WARBM) is a genetic heterogeneous disease characterized by microcephaly, intellectual disability, brain, ocular, and endocrine anomalies. WARBM1-4 can be caused by biallelic mutations of the RAB3GAP1 (RAB3 GTPase-activating protein 1), RAB3GAP2, RAB18 (RAS-associated protein RAB18), or TBC1D20 (TBC1 domain protein, member 20) gene, respectively. Here, we delineate the so far largest intragenic homozygous RAB3GAP1 microdeletion. Despite the size of the RAB3GAP1 gene deletion, the patient phenotype is mainly consistent with that of other WARBM1 patients, supporting strongly the theory that WARBM1 is caused by a loss of RAB3GAP1 function. We further highlight osteopenia as a feature of WARBM1.
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http://dx.doi.org/10.1186/s13023-014-0113-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224754PMC
October 2014