Defining clinical subgroups and genotype–phenotype correlations in NBAS-associated disease across 110 patients

Infantile fever-triggered acute liver failure caused by novel neuroblastoma amplified sequence mutations: a case report

“…Specifically, (c.3386C > T (p.Ser1129Phe), c.1A > C (p.Met1Leu) and c.875G > A (p.Gly292Glu)). Regarding the c.3386C > T (p.Ser1129Phe) mutation, Staufner et al have reported that two patients who harbored this mutation similarly presented ALF without other extrahepatic manifestations [17]. The onset age of those two patients were 2.3 and 1.8 years respectively, close to the age of onset for our patient (2.9 years).…”

“…NBAS mutations have also been identified in SOPH syndrome patients without liver failure [4]. An increasing number of studies have indicated that diseases based on NBAS mutations have a broad phenotypic spectrum, ranging from isolated recurrent ILFS2 to a multi-systemic disease manifesting as short stature, skeletal dysplasia, dysmorphism and optic atrophy with or without liver failure [4][5][6][7][8][9][11][12][13][14][15][16][17][18].…”

“…Moreover, some patients present hepatic encephalopathy or death due to untimely treatment. On the other hand, the main extrahepatic manifestation of NBAS mutations are short stature, skeletal dysplasia, optic atrophy, Pelger-Huët anomaly of granulocytes or immunological abnormalities [7,13,17]. Previous researchers have reported that among the 56 reported patients with NBAS-associated disease, 43 patients (76.8%) presented ILFS2 with multi-systemic manifestations, where short stature was the most common extrahepatic manifestations (34/43, 79.1%).…”

“…The onset age of those two patients were 2.3 and 1.8 years respectively, close to the age of onset for our patient (2.9 years). Staufner et al indicated that the c.3386C > T (p.Ser1129Phe) mutation affected the region coding for the Sec39 domain of the NBAS gene, which is necessary for tethering at the endoplasmic reticulum (ER) in the syntaxin18 [17]. The c.1A > C (p.Met1Leu) mutation is a likely pathogenic mutation (90% pathogenicity) according to the guidelines of the ACMG.…”

NBAS disease: 14 new patients, a recurrent mutation, and genotype–phenotype correlation among 24 Chinese patients

“…3 Since NBAS was first reported to be associated with short stature with optic nerve atrophy and Pelger-Huët anomaly (SOPH) syndrome in 2010, 4 a total of 110 patients with NBAS mutation-related disease have been reported. 5 Clinical manifestations were highly variable ranging from SOPH syndrome, isolated fever-triggered acute liver failure (ALF), to a multisystemic disease involving liver, skeletal, brain, connective tissue, and the immune system resembling an intermediate phenotype. [6][7][8][9][10][11][12][13][14][15][16] The phenotype-genotype correlation study of 110 patients has illustrated that the main clinical features of patients with NBAS biallelic mutations could be dependent on the location of missense and in-frame deletion/insertion mutations in the NBAS protein domain, 5 but whether this correlation also applies to Chinese patients remains to be determined.…”