Familial X-linked mental retardation and isolated growth hormone deficiency: Clinical and molecular findings

Hamel, B.C.J.; Smits, A.P.T.; Otten, B. J.; Helm, L.J.M. van den; Ropers, Hans Hilger; Mariman, E.C.M.

doi:10.1002/(sici)1096-8628(19960712)64:1<35::aid-ajmg5>3.0.co;2-q

Cited by 59 publications

(36 citation statements)

References 13 publications

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“…The genomic sequences (GenBank accession numbers AL034411 and Z96810) were assigned to chromosome X at positions Xq24 and Xq22.1-23, respectively. Interestingly, several forms of nonspecific mental retardation and other central nervous system disorders have been mapped to this region (55)(56)(57)(58)(59)(60)(61)(62).…”

Section: Methodsmentioning

confidence: 99%

Cloning and Functional Expression of a Human Na+and Cl−-dependent Neutral and Cationic Amino Acid Transporter B0+

Sloan

Mager

1999

Journal of Biological Chemistry

308

297

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A Na؉ -dependent neutral and cationic amino acid transport system (B 0؉) plays an important role in many cells and tissues; however, the molecular basis for this transport system is still unknown. To identify new transporters, the expressed sequence tag database was queried, and cDNA fragments with sequence similarity to the Na ؉ /Cl ؊ -dependent neurotransmitter transporter family were identified. Based on these sequences, rapid amplification of cDNA ends of human mammary gland cDNA was used to obtain a cDNA of 4.5 kilobases (kb). The open reading frame encodes a 642-amino acid protein named amino acid transporter B 0؉ . Human ATB 0؉(hATB 0؉ ) is a novel member of the Na ؉ /Cl ؊ -dependent neurotransmitter transporter family with the highest sequence similarity to the glycine and proline transporters. Northern blot analysis identified transcripts of ϳ4.5 kb and ϳ2 kb in the lung. Another tissue survey suggests expression in the trachea, salivary gland, mammary gland, stomach, and pituitary gland. Electrophysiology and radiolabeled amino acid uptake measurements were used to functionally characterize the transporter expressed in Xenopus oocytes. hATB 0؉ was found to transport both neutral and cationic amino acids, with the highest affinity for hydrophobic amino acids and the lowest affinity for proline. Amino acid transport was Na ؉ and Cl ؊ -dependent and was attenuated in the presence of 2-aminobicyclo-[2.2.1]-heptane-2-carboxylic acid, a system B 0؉ inhibitor. These characteristics are consistent with system B 0؉ amino acid transport. Thus, hATB 0؉ is the first cloned B 0؉ amino acid transporter.

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Section: Methodsmentioning

confidence: 99%

Cloning and Functional Expression of a Human Na+and Cl−-dependent Neutral and Cationic Amino Acid Transporter B0+

Sloan

Mager

1999

Journal of Biological Chemistry

308

297

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“…Interestingly, Sox1 -/-mice are characterized by epilepsy [22], which is also known to affect 20%-25% of FXS patients. In addition, patients with SOX3 deficiency show symptoms similar to those observed in FXS patients, characterized by intellectual disability [23,24]. SOX9 is known to play key roles in neural crest development, chondrogenesis, and testis development [25], which are also affected in FXS individuals.…”

Section: Introductionmentioning

confidence: 92%

Molecular Mechanisms Regulating Impaired Neurogenesis of Fragile X Syndrome Human Embryonic Stem Cells

Telias

Mayshar

Amit

et al. 2015

Stem Cells and Development

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Fragile X syndrome (FXS) is the most common form of inherited cognitive impairment. It is caused by developmental inactivation of the FMR1 gene and the absence of its encoded protein FMRP, which plays pivotal roles in brain development and function. In FXS embryos with full FMR1 mutation, FMRP is expressed during early embryogenesis and is gradually downregulated at the third trimester of pregnancy. FX-human embryonic stem cells (FX-hESCs), derived from FX human blastocysts, demonstrate the same pattern of developmentally regulated FMR1 inactivation when subjected to in vitro neural differentiation (IVND). In this study, we used this in vitro human platform to explore the molecular mechanisms downstream to FMRP in the context of early human embryonic neurogenesis. Our results show a novel role for the SOX superfamily of transcription factors, specifically for SOX2 and SOX9, which could explain the reduced and delayed neurogenesis observed in FX cells. In addition, we assess in this study the ''GSK3b theory of FXS'' for the first time in a human-based model. We found no evidence for a pathological increase in GSK3b protein levels upon cellular loss of FMRP, in contrast to what was found in the brain of Fmr1 knockout mice. Our study adds novel data on potential downstream targets of FMRP and highlights the importance of the FX-hESC IVND system.

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“…In humans, tandem duplications involving chromosome Xq26-27 have been identified in several pedigrees with mental retardation and hypopituitarism (36)(37)(38)(39). Using array comparative genomic hybridization, Solomon et al (39) defined a critical duplication region of 3.9 Mb between Xq26.1 and Xq27.3 containing 18 annotated transcripts including SOX3.…”

Section: Sox3mentioning

confidence: 99%

Hypothalamic and pituitary development: novel insights into the aetiology

Kelberman¹,

Dattani²

2007

eur j endocrinol

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The anterior pituitary gland is a central regulator of growth, reproduction and homeostasis, and is the end-product of a carefully orchestrated pattern of expression of signalling molecules and transcription factors leading to the development of this complex organ secreting six hormones from five different cell types. Naturally occurring and transgenic murine models have demonstrated a role for many of these molecules in the aetiology of combined pituitary hormone deficiency (CPHD). These include the transcription factors HESX1, PROP1, POU1F1, LHX3, LHX4, TBX19, SOX2 and SOX3. The expression pattern of these transcription factors dictates the phenotype that results when the gene encoding the relevant transcription factor is mutated. The highly variable phenotype may consist of isolated hypopituitarism, or more complex disorders such as septo-optic dysplasia and holoprosencephaly. Since mutations in any one transcription factor are uncommon, and since the overall incidence of mutations in known transcription factors is low in patients with CPHD, it is clear that many genes remain to be identified, and the characterization of these will further elucidate the pathogenesis of these complex conditions and also shed light on normal pituitary development.European Journal of Endocrinology 157 S3-S14

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Familial X-linked mental retardation and isolated growth hormone deficiency: Clinical and molecular findings

Cited by 59 publications

References 13 publications

Cloning and Functional Expression of a Human Na+and Cl−-dependent Neutral and Cationic Amino Acid Transporter B0+

Cloning and Functional Expression of a Human Na+and Cl−-dependent Neutral and Cationic Amino Acid Transporter B0+

Molecular Mechanisms Regulating Impaired Neurogenesis of Fragile X Syndrome Human Embryonic Stem Cells

Hypothalamic and pituitary development: novel insights into the aetiology

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