An Association of PTPN11 and SHOX Mutations in a Male Presenting With Syndromic Growth Failure

Savarese, Emanuela; Felice, Benedetta Di; Miconi, Francesco; Cabiati, Gabriele; Celi, Federica; Crescenzi, F.; Principi, Nicola; Esposito, Susanna

doi:10.3389/fendo.2018.00557

Cited by 2 publications

(1 citation statement)

References 19 publications

(27 reference statements)

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“…Ogata et al, in their studies in patients with gonadal dysgenesis in association with data on the growth of people with aneuploidy or polysomy of the sex chromosomes, suggested that tall stature can be caused by an additional copy of the SHOX gene with a shortage of oestrogens. 8 , 16 In our study group, one boy was found to have a short stature and low body weight (case 7), while the others with dupXp22.33 showed a rapid growth rate and intellectual disability, which was also found in patient 3. Three (patients 3, 4 and 6) out of five women with identified duplications of Xp22.31 or Xp22.33 reported delayed speech development and learning difficulties in their childhood.…”

Section: Discussionsupporting

confidence: 51%

Clinical Importance of aCGH in Genetic Counselling of Children with Psychomotor Retardation

Pasińska¹,

Łazarczyk²,

Repczyńska³

et al. 2022

TACG

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Introduction The X and Y chromosomes are responsible for the determination and differentiation of the gonads, and their numerical and structural abnormalities may cause the abnormal development of secondary sex characteristics. The presence of abnormalities concerning X chromosome can also contribute to many genetically heterogeneous diseases associated with cognitive impairment and intellectual disability. Purpose This study shows the effect of aberrations of the maternal X chromosome on the abnormal development of the child. Patients and Methods Ten women aged 26 to 40 years were consulted in genetic counselling clinic and subsequently subjected to cytogenetic and molecular tests due to abnormal psychomotor development of their children, in whom structural aberrations of the X chromosome had been detected. Results Two women were diagnosed with changes in karyotype: 46,X,der(X)t(X;Y)(p22.3;q11.2) in one and 46,X,inv(X)(p21.2q13). Five women were diagnosed with microduplications in the short arm of the X chromosome; dupXp22.31 in one, and in four women dupXp22.33. The remaining three women were diagnosed with duplication in the long arm of the X chromosome; dupXq25 in one and dupXq26.3 in two women. Conclusion Genetic analysis of the X chromosome, based on cytogenetic and molecular methods of the highest available resolution, is extremely important in women with reproductive failure. These methods allow establishing accurately the breakpoints and rearrangements in chromosomes, and assessment of the copy number variation (CNV) can explain phenotypic variability with apparently similar aberrations. A more precise characterization of the alterations is necessary for the correct genetic diagnosis, as well as determination of the carrier status and genetic risk in family members.

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Section: Discussionsupporting

confidence: 51%

Clinical Importance of aCGH in Genetic Counselling of Children with Psychomotor Retardation

Pasińska¹,

Łazarczyk²,

Repczyńska³

et al. 2022

TACG

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Integrated in silico MS-based phosphoproteomics and network enrichment analysis of RASopathy proteins

Montero-Bullón

González-Velasco

Isidoro‐García

et al. 2021

Orphanet J Rare Dis

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Background RASopathies are a group of syndromes showing clinical overlap caused by mutations in genes affecting the RAS-MAPK pathway. Consequent disruption on cellular signaling leads and is driven by phosphoproteome remodeling. However, we still lack a comprehensive picture of the different key players and altered downstream effectors. Methods An in silico interactome of RASopathy proteins was generated using pathway enrichment analysis/STRING tool, including identification of main hub proteins. We also integrated phosphoproteomic and immunoblotting studies using previous published information on RASopathy proteins and their neighbors in the context of RASopathy syndromes. Data from Phosphosite database (www.phosphosite.org) was collected in order to obtain the potential phosphosites subjected to regulation in the 27 causative RASopathy proteins. We compiled a dataset of dysregulated phosphosites in RASopathies, searched for commonalities between syndromes in harmonized data, and analyzed the role of phosphorylation in the syndromes by the identification of key players between the causative RASopathy proteins and the associated interactome. Results In this study, we provide a curated data set of 27 causative RASopathy genes, identify up to 511 protein–protein associations using pathway enrichment analysis/STRING tool, and identify 12 nodes as main hub proteins. We found that a large group of proteins contain tyrosine residues and their biological processes include but are not limited to the nervous system. Harmonizing published RASopathy phosphoproteomic and immunoblotting studies we identified a total of 147 phosphosites with increased phosphorylation, whereas 47 have reduced phosphorylation. The PKB signaling pathway is the most represented among the dysregulated phosphoproteins within the RASopathy proteins and their neighbors, followed by phosphoproteins implicated in the regulation of cell proliferation and the MAPK pathway. Conclusions This work illustrates the complex network underlying the RASopathies and the potential of phosphoproteomics for dissecting the molecular mechanisms in these syndromes. A combined study of associated genes, their interactome and phosphorylation events in RASopathies, elucidates key players and mechanisms to direct future research, diagnosis and therapeutic windows.

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An Association of PTPN11 and SHOX Mutations in a Male Presenting With Syndromic Growth Failure

Cited by 2 publications

References 19 publications

Clinical Importance of aCGH in Genetic Counselling of Children with Psychomotor Retardation

Clinical Importance of aCGH in Genetic Counselling of Children with Psychomotor Retardation

Integrated in silico MS-based phosphoproteomics and network enrichment analysis of RASopathy proteins

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