Moyamoya Syndrome in a Patient With Noonan-like Syndrome With Loose Anagen Hair

Choi, Jin‐Ho; Oh, Moon-Yeon; Yum, Mi‐Sun; Lee, Beom Hee; Kim, Gu-Hwan; Yoo, Han‐Wook

doi:10.1016/j.pediatrneurol.2014.11.017

Cited by 21 publications

(10 citation statements)

References 15 publications

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“…Apart from NF1, MMS is a rarely observed in connection with other RASopathies (e.g., a few cases were reported among patients with Noonan syndrome) (Choi et al, ; Ganesan & Kirkham, ; Hung, Wang, & Wong, ; Lo, Wang, Wong, & Lee, ; Schuster & Roberts, ; Tang, Yang, Wong, & Lee, ). This specificity has suggested that MMS pathogenesis in NF1 strongly depends on multiple NF1 activities, rather than simply the disruption of RAS and MAP kinase activities.…”

Section: Discussionmentioning

confidence: 99%

Moyamoya syndrome in children with neurofibromatosis type 1: Italian–French experience

Santoro

Rocco

Kossorotoff

et al. 2017

American J of Med Genetics Pt A

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Moyamoya syndrome (MMS) is the most common cerebral vasculopathy among children with neurofibromatosis type 1 (NF1). In this study, we clinically, radiologically, and genetically examined a cohort that was not previously described, comprising European children with NF1 and MMS. The NF1 genotyping had been registered. This study included 18 children. The mean age was 2.93 ± 3.03 years at the NF1 diagnosis and 7.43 ± 4.27 years at the MMS diagnosis. In seven patients, MMS was diagnosed before or at the same time as NF1. Neuroimaging was performed in 10 patients due to clinical symptoms, including headache (n = 6), cerebral infarction (n = 2), and complex partial seizures (n = 2). The remaining eight children (47%) had MMS diagnosed incidentally. Sixteen children were characterized molecularly. The features of MMS were similar between patients with and without NF1. Additionally, the NF1 phenotype and genotype were similar between children with and without MMS. Interestingly, three children experienced tumors with malignant histology or behavior. The presence of two first cousins in our cohort suggested that there may be potential genetic factors, not linked to NF1, with an additional role respect of NF1 might play a role in MMS pathogenesis. The incidental diagnosis of MMS, and the observation that, among children with NF1, those with MMS were clinically indistinguishable from those without MMS, suggested that it might be worthwhile to add an angiographic sequence to brain MRIs requested for children with NF1. A MMS diagnosis may assist in properly addressing an NF1 diagnosis in very young children who do not fulfill diagnostic criteria.

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Section: Discussionmentioning

confidence: 99%

Moyamoya syndrome in children with neurofibromatosis type 1: Italian–French experience

Santoro

Rocco

Kossorotoff

et al. 2017

American J of Med Genetics Pt A

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“…Given that developmental processes crucially rely on tightly controlled signaling activities, aberrations in the mechanisms that control the timing and amplitude of ERK1/2 signals will have important implications in development. Not surprisingly, alterations in this intricate mechanism due to the Shoc2-S2G mutation cause RASopathy with pathological conditions ranging from distinctive craniofacial dysmorphisms and a wide spectrum of congenital heart defects to variable neurocognitive impairments, brain anomalies and Moyamoya syndrome (Capalbo et al, 2012;Choi et al, 2015;Gripp et al, 2013;Hoban et al, 2012).…”

Section: Functional Implications Of Psmc5-modulated Ubiquitylation Ofmentioning

confidence: 99%

Spatial control of Shoc2 scaffold-mediated ERK1/2 signaling requires remodeling activity of the ATPase PSMC5

Jang

Shi

et al. 2015

Journal of Cell Science

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The scaffold protein Shoc2 accelerates activity of the ERK1 and ERK2 (ERK1/2, also known as MAPK3 and MAPK1) pathway. Mutations in Shoc2 result in Noonan-like RASopathy, a developmental disorder with a wide spectrum of symptoms. The amplitude of the ERK1/2 signals transduced through the complex is fine-tuned by the HUWE1-mediated ubiquitylation of Shoc2 and its signaling partner RAF-1. Here, we provide a mechanistic basis of how ubiquitylation of Shoc2 and RAF-1 is controlled. We demonstrate that the newly identified binding partner of Shoc2, the (AAA+) ATPase PSMC5, triggers translocation of Shoc2 to endosomes. At the endosomes, PSMC5 displaces the E3 ligase HUWE1 from the scaffolding complex to attenuate ubiquitylation of Shoc2 and RAF-1. We show that a RASopathy mutation that changes the subcellular distribution of Shoc2 leads to alterations in Shoc2 ubiquitylation due to the loss of accessibility to PSMC5. In summary, our results demonstrate that PSMC5 is a new and important player involved in regulating ERK1/2 signal transmission through the remodeling of Shoc2 scaffold complex in a spatially-defined manner.

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“…Individuals with NSLH1 are more likely to have intellectual disability, relative macrocephaly, sparse/loose anagen hair, and growth hormone deficiency (GHD) compared to individuals with Noonan syndrome (NS) caused by mutations in other genes. The clinical features of 84 patients with NSLH1 have been described (Table ) (Bader‐Meunier et al, ; Capalbo, Melis, et al, ; Capalbo, Scala, et al, ; Choi et al, ; Cordeddu et al, ; Ekvall, Hagenäs, Allanson, Annerén, & Bondeson, ; Ferrero et al, ; Garavelli et al, ; Gargano et al, ; Gripp et al, ; Hoban, Roberts, Demmer, Jethva, & Shephard, ; Kane et al, ; Komatsuzaki et al, ; Lo, Wang, Wong, & Lee, ; Mazzanti et al, ; Mazzanti et al, ; Şimşek‐Kiper et al, ; Tafazoli, Eshraghi, Koleti, & Abbaszadegan, ; Takenouchi et al, ; Tartaglia, Zampino, & Gelb, ; Tosti et al, ; Tosti et al, ; Tosti & Piraccini, ; Zmolikova et al, ). With the possible exception of one patient with unusual but not well‐defined palatal anatomy (Kumar, Chandar, Koduri, & Sankireddy, ), posterior cleft palate (CP) has not been reported in individuals with NS or with NSLH (Cao, Alrejaye, Klein, Goodwin, & Oberoi, ; Mallineni, Yung Yiu, & King, ).…”

Section: Introductionmentioning

confidence: 99%

Cleft palate and hypopituitarism in a patient with Noonan‐like syndrome with loose anagen hair‐1

Couser

Keelean‐Fuller

Davenport

et al. 2018

American J of Med Genetics Pt A

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Noonan syndrome (NS), the most common of the RASopathies, is a developmental disorder caused by heterozygous germline mutations in genes encoding proteins in the RAS‐MAPK signaling pathway. Noonan‐like syndrome with loose anagen hair (NSLH, including NSLH1, OMIM #607721 and NSLH2, OMIM #617506) is characterized by typical features of NS with additional findings of macrocephaly, loose anagen hair, growth hormone deficiency in some, and a higher incidence of intellectual disability. All NSLH1 reported cases to date have had an SHOC2 c.4A>G, p.Ser2Gly mutation; NSLH2 cases have been reported with a PPP1CB c.146G>C, p.Pro49Arg mutation, or c.166G>C, p.Ala56Pro mutation. True cleft palate does not appear to have been previously reported in individuals with NS or with NSLH. While some patients with NS have had growth hormone deficiency (GHD), other endocrine abnormalities are only rarely documented. We present a female patient with NSLH1 who was born with a posterior cleft palate, micrognathia, and mild hypotonia. Other findings in her childhood and young adulthood years include hearing loss, strabismus, and hypopituitarism with growth hormone, thyroid stimulating hormone (TSH), and gonadotropin deficiencies. The SHOC2 mutation may be responsible for this patient's additional features of cleft palate and hypopituitarism.

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Moyamoya Syndrome in a Patient With Noonan-like Syndrome With Loose Anagen Hair

Cited by 21 publications

References 15 publications

Moyamoya syndrome in children with neurofibromatosis type 1: Italian–French experience

Moyamoya syndrome in children with neurofibromatosis type 1: Italian–French experience

Spatial control of Shoc2 scaffold-mediated ERK1/2 signaling requires remodeling activity of the ATPase PSMC5

Cleft palate and hypopituitarism in a patient with Noonan‐like syndrome with loose anagen hair‐1

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