Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in spectrin beta non-erythrocytic 4 (SPTBN4) have been linked to congenital hypotonia, intellectual disability and motor neuropathy. Here we report on two siblings with a homozygous splice-site mutation in the SPTBN4 gene, lacking previously reported features of the disorder such as seizures, feeding difficulties, respiratory difficulties or profound intellectual disability. Our findings indicate that muscular hypotonia, myopathic facies with ptosis and axonal neuropathy can be the core clinical features in the SPTBN4 disorder and suggest that SPTBN4 mutation analysis should be considered in infants with marked axonal neuropathy.
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PMID:A novel homozygous splice-site mutation in the SPTBN4 gene causes axonal neuropathy without intellectual disability. 3185 55

Immune checkpoint inhibitors (ICI) have altered the prognosis of patients with melanoma over the past few years, with immune-related adverse effects (irAEs) being the only factor limiting their use. Neurologic and cardiac irAEs are rare, but usually severe. We reviewed the files of patients with melanoma treated with ICIs in one center to retrieve data from patients with neurologic irAEs. Patients with a combination of neurologic and cardiac manifestations were further analyzed. We also reviewed the literature for similar syndromes. Five out of 482 (1.01%) patients developed a neurologic syndrome and we present three patients with a constellation of neurologic and cardiac irAEs. A 66-year-old woman and a 68-year-old man presented with a constellation of findings after being treated with ipilimumab and nivolumab, respectively, for melanoma in the adjuvant setting and were eventually diagnosed with myasthenia gravis with cardiac involvement. An 80-year-old woman developed diffuse asymmetric muscle weakness, bilateral ptosis and asymptomatic high serum troponin levels after adjuvant treatment with nivolumab and ipilimumab for a stage IIIB melanoma. After excluding ischemic heart disease, she was diagnosed with axonal polyradiculoneuropathy and myocarditis. Neurologic or cardiac irAEs in patients treated with ICIs are uncommon (<1%), but usually severe, with high rates of morbidity and fatality. The co-development of neurologic and cardiac irAEs is even more rare and can arise soon after exposure to ICIs and escalate rapidly. Since more and more patients are now treated with ICIs in the adjuvant setting, prompt identification and management are essential to avoid serious complications or death.
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PMID:Concomitant development of neurologic and cardiac immune-related adverse effects in patients treated with immune checkpoint inhibitors for melanoma. 3289 89

Variants in MCM3AP, encoding the germinal-centre associated nuclear protein, have been associated with progressive polyneuropathy with or without intellectual disability and ptosis in some cases, and with a complex phenotype with immunodeficiency, skin changes and myelodysplasia. MCM3AP encoded protein functions as an acetyltransferase that acetylates the replication protein, MCM3, and plays a key role in the regulation of DNA replication. In this study, we report a novel variant in MCM3AP (p.Ile954Thr), in a family including three affected individuals with characteristic features of Charcot-Marie-Tooth neuropathy and multiple sclerosis, an inflammatory condition of the central nervous system without known genetic cause. The affected individuals were homozygous for a missense MCM3AP variant, located at the Sac3 domain, which was predicted to affect conserved amino acid likely important for the function of the germinal-centre associated nuclear protein. Our data support further expansion of the clinical spectrum linked to MCM3AP variant and highlight that MCM3AP should be considered in patients with accompaniment of recessive motor axonal Charcot-Marie-Tooth neuropathy and multiple sclerosis.
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PMID:Recessive Charcot-Marie-Tooth and multiple sclerosis associated with a variant in MCM3AP. 3295 58


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