Germline mosaicism in Coffin-Lowry syndrome

Jacquot, Sylvie; Mérienne, Karine; Pannetier, Solange; Blumenfeld, Sandra; Schinzel, Albert; Hanauer, André

doi:10.1038/sj.ejhg.5200230

Cited by 14 publications

(16 citation statements)

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“…The latter included 59 families with sporadic cases and four families with two or three affected siblings. Evidence for gonadal mosaicism was clearly shown in the latter four families (Jacquot et al, 36 Horn et al, 37 and A Hanauer unreported observations). This result suggests that germline mutation mosaicism is not uncommon and that the recurrence risk in families with a single affected child with CLS, even when the mother is negative for a mutation, may be significant.…”

Section: Genetic Counselingmentioning

confidence: 99%

Coffin–Lowry syndrome

et al. 2009

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Coffin-Lowry syndrome (CLS) is a syndromic form of X-linked mental retardation, which is characterized in male patients by psychomotor and growth retardation and various skeletal anomalies. Typical facial changes and specific clinical and radiological signs in the hand are useful aids in the diagnosis. CLS is caused by mutations in the RPS6KA3 gene located at Xp22.2, which encodes RSK2, a growth-factor-regulated protein kinase. RPS6KA3 mutations are extremely heterogeneous and lead to loss of phosphotransferase activity in the RSK2 kinase, most often because of premature termination of translation.

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Section: Genetic Counselingmentioning

confidence: 99%

Coffin–Lowry syndrome

et al. 2009

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“…This fact, combined with their wide but distinct tissue distribution (33), suggests that RSK proteins are involved in the regulation of critical and different functions in the organism. Despite extensive studies during more than a decade, the physiological roles of specific RSK proteins remain elusive.Recently, it was discovered that mutations in the human rsk2 gene cause a rare form of the X-linked mental retardation syndrome known as the Coffin-Lowry syndrome (CLS) (34,35). Patients with CLS are characterized by psychomotor retardation, progressive skeletal deformations, and short stature (36 -38).…”

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confidence: 99%

“…Recently, it was discovered that mutations in the human rsk2 gene cause a rare form of the X-linked mental retardation syndrome known as the Coffin-Lowry syndrome (CLS) (34,35). Patients with CLS are characterized by psychomotor retardation, progressive skeletal deformations, and short stature (36 -38).…”

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confidence: 99%

Insulin Resistance and Lipodystrophy in Mice Lacking Ribosomal S6 Kinase 2

et al. 2003

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The p90 ribosomal S6 kinase 2 (RSK2) is a serine/ threonine kinase with high expression levels in adipose tissue. Numerous in vitro studies show that RSK2 is activated by a broad number of cellular stimuli and suggest that RSK2 is involved in the regulation of a variety of cellular processes. However, the physiological role of RSK2 still remains elusive. We therefore generated rsk2 knockout (KO) mice to better understand the function of RSK2 in vivo. Birth weights of RSK2 KO mice are normal, but the body weight is reduced with age, as compared with wild-type littermates. We found that the difference in body weight was largely caused by a specific loss of white adipose tissue that is accompanied by reduced serum levels of the adipocyte-derived peptide, leptin. KO mice also have impaired glucose tolerance and elevated fasting insulin and glucose levels that are restored following administration of low amounts of leptin, which do not affect food intake. We conclude that RSK2 plays a novel and an important role in regulation of adipose mass in mice and speculate that the reduction in fat tissue may negatively affect insulin sensitivity, as observed in human lipodystrophy, through reduced levels of adipocyte-derived factors, such as leptin. Diabetes 52:1340 -1346, 2003 R SK2 is a member of a family of growth factorregulated serine-threonine kinases known as p90rsk (90-kDa ribosomal S6 kinase) or as mitogen-activated protein (MAP) kinase-activated protein kinase 1 (MAPKAP-K1b) (1-6). Several mammalian isoforms of RSK (RSK1-4) have been identified in different species (7-10). In addition, novel proteins that are homologous to RSK have recently been discovered, including mitogen-and stress-activated protein kinase (MSK) and 11,12). RSK enzymes are activated in response to a variety of cellular stimuli, growth factors, and hormones, including epidermal growth factor, insulin, phorbol-esters, heat shock, and ionizing radiation (1,13-17). The activation is complex and requires phosphorylation at multiple sites by different upstream kinases, including the p42 and p44 MAP kinases, and the 3-phosphoinositide-dependent protein kinase 1 (18,19). RSK proteins contain two distinct kinase domains that set them apart from most other protein kinases (3). After phosphorylation by the upstream kinases, the COOH-terminal kinase domain of RSK autophosphorylates additional sites in the RSK molecule, ultimately resulting in activation of the NH 2 -terminal kinase domain, which is responsible for substrate phosphorylation (20 -24). RSK enzymes have broad substrate specificity (25), and putative substrates include nuclear proteins and transcription factors such as cAMP-responsive binding-element protein (26,27), lamin-C (28), histone 3B (29), c-fos (26), glycogen synthase kinase 3 (30), BAD (31), and IB/NFB (32). Based on these findings, RSK proteins are likely to regulate a variety of cellular processes. This fact, combined with their wide but distinct tissue distribution (33), suggests that RSK proteins are involved in the regulation of c...

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“…Hunter et al 10 estudaram 16 famílias, sendo que em apenas seis havia mais de um indivíduo afetado; as demais fizeram-se representar por um único portador da síndrome, fato provavelmente decorrente de novas mutações. Recentemente Jacquot et al 22 estudaram uma família na qual, de quatro filhos, dois eram normais e dois apresentavam mutações no DNA e características clínicas da SCL. O DNA das células somáticas (linfócitos) da mãe não apresentava indícios de mutação.…”

Section: Relato Do Casounclassified

Coffin-Lowry syndrome

Guitti

Peres²

2000

J Pediatr (Rio J)

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ResumoObjetivo: Colaborar para a disseminação do conhecimento da síndrome de Coffin-Lowry e contribuir para o delineamento da mesma.Métodos: Relato de caso. Resultados:São descritos e comentados os sinais clínicos de um paciente com síndrome de Coffin-Lowry.Conclusões: A síndrome de Coffin-Lowry, doença genética com herança ligada ao cromossomo X, é provavelmente subdiagnosticada no Brasil. Facies característica, anomalias dento-esqueléticas e retardo mental sugerem o diagnóstico, que pode ser comprovado clinicamente pela radiografia das mãos.J. pediatr. (Rio J.). 2000; 76(4):305-309: retardo mental, alterações esqueléticas, anomalias dentárias. AbstractObjective: To promote the diffusion of the knowledge on the Coffin-Lowry syndrome and to contribute to the outline of the disease.Methods: Case report. Results:The clinical signs of a patient with the Coffin-Lowry syndrome are described and discussed.Conclusions: The Coffin-Lowry syndrome, a X-linked genetic disease, is probably underdiagnosed in Brazil. The typical facies, dental-skeletal anomalies and mental retardation suggest the diagnosis, which can be clinically established by radiographic study of the hands. Embora a facies de seus portadores seja típica, é prová-vel que a SCL esteja sendo subdiagnosticada, possivelmente porque os médicos generalistas não estejam devidamente treinados para a realização de exame dismorfológico. Evidência dessa possibilidade é não haver qualquer referência sobre publicação na América Latina (Medline, Lilacs), exceto o relato de dois casos no México 8 . J. pediatr. (Rio J. Relato do casoCriança com 9 anos e 3 meses, sexo masculino, branco, procedente de Londrina (Paraná). Produto da única gestação em casal não consanguíneo, nascido de parto normal eutócico (peso: 3.100g; comprimento: 49cm; perímetro cefálico e torácico: 34cm e 33cm, respectivamente), sem intercorrências no período neonatal. A partir do 10º mês de vida tornaram-se aparentes traços faciais grosseiros e retardo do desenvolvimento neuropsicomotor, que se acentua-

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Germline mosaicism in Coffin-Lowry syndrome

Cited by 14 publications

References 18 publications

Coffin–Lowry syndrome

Coffin–Lowry syndrome

Insulin Resistance and Lipodystrophy in Mice Lacking Ribosomal S6 Kinase 2

Coffin-Lowry syndrome

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