A case report of Noonan syndrome‐like disorder with loose anagen hair 2 treated with recombinant human growth hormone

Zhou, Ping; Zhu, Lin; Fan, Qiong-Li; Liu, Yongfang; Tian-xiu, Zhang; Yang, Ting; Chen, Jie; Qian, Cheng; Li, Tingyu; Chen, Li

doi:10.1002/ajmg.a.61638

Cited by 4 publications

(6 citation statements)

References 21 publications

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“…While the majority of studies on PP1 in synaptic plasticity have focused on neurabin and spinophilin, which preferentially bind PP1γ and PP1α, recent evidence suggests PP1β has a significant but ill-defined role in neuronal physiology. Several groups have discovered human de novo mutations in PP1β associated with severe intellectual disability (Gripp et al, 2016; Hamdan et al, 2014; Huckstadt et al, 2021; Lin et al, 2018; Ma et al, 2016; Umeki et al, 2019; Zambrano et al, 2017; Zhou et al, 2020), with none yet identified in PP1α and PP1γ. Further, mRNA expression data suggest PP1β could promote learning and memory: high-performing rodents in the Morris Water Maze have significantly lower levels of PP1γ (Haege et al, 2010) but higher levels of PP1β (Burger et al, 2007) in the hippocampus compared to poor-performing rodents.…”

Section: Introductionmentioning

confidence: 99%

PP1β opposes classic PP1 function, inhibiting spine maturation and promoting LTP

Foley

McKee

Ganguly

et al. 2023

Preprint

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Protein phosphatase 1 (PP1) regulates synaptic plasticity and has been described as a molecular constraint on learning and memory. There are three neuronal isoforms, PP1α, PP1β, and PP1γ, but little is known about their individual functions. PP1α and PP1γ are assumed to mediate the effects of PP1 on learning and memory based on their enrichment at dendritic spines and their preferential binding to neurabin and spinophilin, major PP1 synaptic scaffolding proteins. However, it was recently discovered that human de novo PP1β mutations cause intellectual disability, suggesting an important but ill-defined role for PP1β. In this study, we investigated the functions of each PP1 isoform in hippocampal synaptic physiology using conditional CA1-specific knockout mice. In stark contrast to classic PP1 function, we found that PP1β promotes synaptic plasticity as well as spatial memory. These changes in synaptic plasticity and memory are accompanied by changes in GluA1 phosphorylation, GluN2A levels, and dendritic spine density and morphology, including silent synapse number. These functions of PP1β reveal a previously unidentified signaling pathway regulating spine maturation and plasticity, broadening our understanding of the complex role of PP1 in synaptic physiology.

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Section: Introductionmentioning

confidence: 99%

PP1β opposes classic PP1 function, inhibiting spine maturation and promoting LTP

Foley

McKee

Ganguly

et al. 2023

Preprint

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“…At present, 16 cases of PPP1CB gene mutation type 2 Noonan-like syndrome associated with birth hair loosening have been reported worldwide. Of these, two cases are reported in China (Zhou et al, 2020); ours is the third reported case in China. As shown in Table 1, there are seven types of gene mutations reported in 16 patients (Matozaki et al, 2009;Zambrano et al, 2017;Lin et al, 2018;Zhou et al, 2020;Maruwaka, 2022;21).…”

Section: Discussionmentioning

confidence: 88%

“…Of these, two cases are reported in China (Zhou et al, 2020); ours is the third reported case in China. As shown in Table 1, there are seven types of gene mutations reported in 16 patients (Matozaki et al, 2009;Zambrano et al, 2017;Lin et al, 2018;Zhou et al, 2020;Maruwaka, 2022;21). c.146C>G (p.Pro49Arg) is the hot spot of PPP1CB gene mutations (Zambrano et al, 2017).…”

Section: Discussionmentioning

confidence: 88%

“…In 2007, the guidelines of the US Food and Drug Administration and the Pediatric Endocrinology, Genetics, and Metabolism Group of the Chinese Medical Association used recombinant human growth hormone (rhGH) for the treatment of short stature caused by Noonan syndrome (Degirmenci et al, 2020 ). In 2020, a study used rhGH to treat a patient with NSLH2 type 2 caused by PPP1CB mutation, and the results showed that the linear growth of the patient had improved (Zhou et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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Case report: Identification and clinical phenotypic analysis of novel mutation of the PPP1CB gene in NSLH2 syndrome

Wang

et al. 2022

Front. Behav. Neurosci.

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ObjectiveTo screen and analyze the genetic mutations in the PPP1CB gene in a patient with Noonan syndrome with loose anagen hair-2 (NSLH2) in Yunnan Province, China and explore the possible molecular pathogenesis.MethodsAfter obtaining informed consent, we collected the patient's medical history and carried out physical and laboratory examinations for the NSLH2 proband and the family members. Genomic DNA was extracted from the peripheral blood of all individuals. The coding regions including all pathogenic exons, parts of introns, and promoters of genes were sequenced by next-generation sequencing. Pathogenic mutations, which were detected in the probands and their parents, were verified by Sanger sequencing.ResultsThe clinical manifestations of NSLH2 included prominent forehead, yellowish hair, slightly wide eye distance, sparse eyebrows, bilateral auricle deformity, reduced muscle tension, and cardiac and visual abnormalities. The proband carried a c.371A>G mutation in exon 3 of PPP1CB, which is a missense mutation. This was a de novo mutation as the parents of the proband showed no mutation at this site.ConclusionIn this study, we identified a novel mutation of PPP1CB, which enriched the mutation spectrum of the PPP1CB gene and provided a basis for the diagnosis of NSLH2.

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“…(Zambrano et al, 2017). Although a number of Noonan syndrome and NSLH1 patients have shown blunted or no response to GH therapy, GH therapy improved the linear growth of NSLH2 patient without GHD (Zhou et al, 2020). In our patient 1, rhGH therapy improved his height velocity.…”

Section: Discussionmentioning

confidence: 99%

Two Japanese patients with Noonan syndrome‐like disorder with loose anagen hair 2

Maruwaka

Nakajima

Yamada

et al. 2022

American J of Med Genetics Pt A

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Noonan syndrome‐like disorder with loose anagen hair (NSLH) is a rare disease characterized by typical features of Noonan syndrome with additional findings of relative or absolute macrocephaly, loose anagen hair, and a higher incidence of intellectual disability. NSLH1 is caused by a heterozygous mutation in the SHOC2 gene on chromosome 10q25, and NLSH2 is caused by a heterozygous mutation in the Protein phosphatase one catalytic subunit beta (PPP1CB) gene on chromosome 2p23. Protein phosphatase1 (PP1), encoded by PPP1CB, forms a complex with SHOC2 and dephosphorylates RAFs, which results in activation of the signaling cascade and contribution to Noonan syndrome pathogenesis. Here, we report two genetically confirmed Japanese patients with NSLH2 having the same de novo mutation in PPP1CB presenting prominent—hyperteloric—appearing eyes and a tall forehead similar to individuals carrying a mutation in PPP1CB, c.146C > G; p.Pro49Arg, which is different from typical facial features of Noonan syndrome. They also showed short stature, absolute macrocephaly, and loose anagen hair like NSLH1: however, growth hormone deficiency often seen in NSLH1 caused by SHOC2 mutation was absent. Although a number of Noonan syndrome and NSLH1 patients have shown blunted or no response to GH therapy, linear growth was promoted by recombinant human growth hormone (rhGH) in one of our patients. Since another NSLH2 patient with good response to rhGH treatment was reported, rhGH therapy may be effective in patients with NSLH2.

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A case report of Noonan syndrome‐like disorder with loose anagen hair 2 treated with recombinant human growth hormone

Cited by 4 publications

References 21 publications

PP1β opposes classic PP1 function, inhibiting spine maturation and promoting LTP

PP1β opposes classic PP1 function, inhibiting spine maturation and promoting LTP

Case report: Identification and clinical phenotypic analysis of novel mutation of the PPP1CB gene in NSLH2 syndrome

Two Japanese patients with Noonan syndrome‐like disorder with loose anagen hair 2

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