Genome-first approach for the characterization of a complex phenotype with combined NBAS and CUL4B deficiency

Ritelli, Marco; Palagano, Eleonora; Cinquina, Valeria; Beccagutti, Federica; Chiarelli, Nicola; Strina, Dario; Hall, Ignacio Fernando; Villa, Anna; Sobacchi, Cristina; Colombi, Marina

doi:10.1016/j.bone.2020.115571

Cited by 8 publications

(6 citation statements)

References 80 publications

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“…12 Absence of the CUL4B protein has been linked to structural or functional abnormalities in the central nervous, skeletal, and hematopoietic systems, indicating that CUL4B plays a critical role in many aspects of human development. 13 The mutation in our patient converts a codon for arginine into a premature termination codon (p.R408X), rendering a truncated protein lacking the A-terminal catalytic domain and triggering nonsense-mediated mRNA decay. 12 Mutations in CUL4B have been identified in some patients with Xlinked mental retardation, but we are unaware of reports linking it to CAPNON or to tumorigenesis.…”

Section: Discussionmentioning

confidence: 87%

“…This gene encodes a scaffold protein that helps organization of the cullin‐RING ubiquitin ligase (E3) complex 12 . Absence of the CUL4B protein has been linked to structural or functional abnormalities in the central nervous, skeletal, and hematopoietic systems, indicating that CUL4B plays a critical role in many aspects of human development 13 . The mutation in our patient converts a codon for arginine into a premature termination codon (p.R408X), rendering a truncated protein lacking the A‐terminal catalytic domain and triggering nonsense‐mediated mRNA decay 12 .…”

Section: Discussionmentioning

confidence: 99%

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Calcifying pseudoneoplasms of the neuraxis (CAPNON). A case report

Wang

Zhang

et al. 2021

Neuropathology

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Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, slow-growing, benign lesions occurring throughout the neuroaxis that are frequently misdiagnosed and overlooked by clinicians. Here, we report a case of a 56-year-old woman who presented with a history of recurrent headache for the previous six years. Magnetic resonance imaging (MRI) revealed a 2.3-cm-sized solid mass in the right frontal lobe that was surrounded by marked edematous areas. The lesion demonstrated dense calcification and avid enhancement. The lesion was initially diagnosed as oligodendroglioma, and then found to be CAPNON based on histopathology of a surgically resected tissue. Genetic analysis revealed a nonsense mutation in the CUL4B gene. The patient's condition appeared to reflect a reactive, rather than neoplastic, process. Clinicians should be prepared to detect such pseudotumors histopathologically in order to avoid unnecessary differential tests of neoplastic or infectious diseases, as well as potentially harmful therapies.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Calcifying pseudoneoplasms of the neuraxis (CAPNON). A case report

Wang

Zhang

et al. 2021

Neuropathology

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“…A significant decrease in collagen secretion by cells with the mutant construct was identified compared with controls. It was concluded that NBAS plays a key role in the formation of large vesicles through the secretory pathway by interacting with TANGO1 28,29 . But since fibroblasts do not contain large enough structures to incorporate collagen (COPII is too small), another study showed that TGF‐β1 (transforming growth factor β1) upregulated the secretion of pro‐COL Iα1 in the culture supernatants and increased the colocalization of COL I with Rab8a, a marker of secretory autophagy vesicles 30 .…”

Section: Discussionmentioning

confidence: 99%

Origins of SOPH syndrome: A study of 93 Yakut patients with review of C‐terminal phenotype

Zhozhikov

Syromyatnikova

Gurinova³

et al. 2023

Clinical Genetics

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Since the first report of SOPH syndrome among the Yakut population in 2010, new clinical data of SOPH-like conditions continue to appear. We expand the phenotypic spectrum of SOPH syndrome and perform a comparative analysis of Yakut SOPH patients' clinical data with SOPH-like conditions reported in the world scientific literature to form a foundation for NBAS pathogenesis discussion. Clinical data from the genetic records of 93 patients with SOPH syndrome and global survey data on patients with pathogenic variants of the C-terminal in the NBAS gene were collected.A detailed phenotype description of patients is presented with a total number of 111 individuals. Underweight below the fifth centile and prone to delayed bone age in Yakut SOPH patients are retrospectively observed. We outline the short stature with optic atrophy as the leading phenotyping trait for C-terminal NBAS patients. The pathophysiology and patients management of SOPH-like conditions are discussed.

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“…By now, there is a total number of over 130 published cases of NBAS-associated disease worldwide. [4][5][6][7][8] There are three clinical subgroups of NBASassociated disease that are related to the affected protein domains 4 : patients with missense variants affecting the Sec 39 domain present with a predominantly hepatic phenotype, characterized by recurrent ALF triggered by febrile infections, named infantile liver failure syndrome type 2 (ILFS2; MIM: 616483). Patients with missense variants affecting the C-terminal protein segment show a multisystemic phenotype involving growth, skeleton, integument, immune system, nervous system, endocrine system, eye, and liver.…”

Section: Introductionmentioning

confidence: 99%

“…In 2015, biallelic pathogenic NBAS variants were found in several patients with recurrent acute liver failure (ALF) triggered by febrile infections. By now, there is a total number of over 130 published cases of NBAS‐associated disease worldwide 4–8 …”

Section: Introductionmentioning

confidence: 99%

Pregnancy, delivery, and postpartum period in infantile liver failure syndrome type 2 due to variants in NBAS

et al. 2023

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Biallelic pathogenic variants in the neuroblastoma amplified sequence (NBAS) gene affecting the Sec39 domain are associated with a predominant hepatic phenotype named infantile liver failure syndrome type 2 (ILFS2). Individuals are at risk of developing life‐threatening acute liver failure episodes, most likely triggered by febrile infections. Pregnancy, delivery, and the postpartum period are well known triggers of decompensation in different inherited metabolic diseases and therefore entail a potential risk also for individuals with ILFS2. We studied pregnancy, birth, and postpartum period in a woman with ILFS2 (homozygous for the NBAS variant c.2708 T > G, p.(Leu903Arg)). During two pregnancies there were no complications associated with the underlying genetic condition. Two healthy boys were born by cesarean section. To reduce the risk of fever and febrile infections, we avoided prolonged labor, epidural analgesia, and breastfeeding. Maternal body temperature and liver function were closely monitored. In case of elevated body temperature, antipyretic treatment (acetaminophen, metamizole) was given without delay. Alanine and aspartate aminotransferases as well as liver function remained normal throughout the observation period. Hence, pregnancy and childbirth are feasible in women with ILFS2 under careful monitoring.

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Genome-first approach for the characterization of a complex phenotype with combined NBAS and CUL4B deficiency

Cited by 8 publications

References 80 publications

Calcifying pseudoneoplasms of the neuraxis (CAPNON). A case report

Calcifying pseudoneoplasms of the neuraxis (CAPNON). A case report

Origins of SOPH syndrome: A study of 93 Yakut patients with review of C‐terminal phenotype

Pregnancy, delivery, and postpartum period in infantile liver failure syndrome type 2 due to variants in NBAS

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