ABCA3 p.Tyr1515*
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[hide] Genotype-phenotype correlations for infants and ch... Am J Respir Crit Care Med. 2014 Jun 15;189(12):1538-43. doi: 10.1164/rccm.201402-0342OC. Wambach JA, Casey AM, Fishman MP, Wegner DJ, Wert SE, Cole FS, Hamvas A, Nogee LM
Genotype-phenotype correlations for infants and children with ABCA3 deficiency.
Am J Respir Crit Care Med. 2014 Jun 15;189(12):1538-43. doi: 10.1164/rccm.201402-0342OC., [PMID:24871971]
Abstract [show]
RATIONALE: Recessive mutations in the ATP-binding cassette transporter A3 (ABCA3) cause lethal neonatal respiratory failure and childhood interstitial lung disease. Most ABCA3 mutations are private. OBJECTIVES: To determine genotype-phenotype correlations for recessive ABCA3 mutations. METHODS: We reviewed all published and unpublished ABCA3 sequence and phenotype data from our prospective genetic studies of symptomatic infants and children at Washington and Johns Hopkins Universities. Mutations were classified based on their predicted disruption of protein function: frameshift and nonsense mutations were classified as "null," whereas missense, predicted splice site mutations, and insertion/deletions were classified as "other." We compared age of presentation and outcomes for the three genotypes: null/null, null/other, and other/other. MEASUREMENTS AND MAIN RESULTS: We identified 185 infants and children with homozygous or compound heterozygous ABCA3 mutations and lung disease. All of the null/null infants presented with respiratory failure at birth compared with 75% of infants with null/other or other/other genotypes (P = 0.00011). By 1 year of age, all of the null/null infants had died or undergone lung transplantation compared with 62% of the null/other and other/other children (P < 0.0001). CONCLUSIONS: Genotype-phenotype correlations exist for homozygous or compound heterozygous mutations in ABCA3. Frameshift or nonsense ABCA3 mutations are predictive of neonatal presentation and poor outcome, whereas missense, splice site, and insertion/deletions are less reliably associated with age of presentation and prognosis. Counseling and clinical decision making should acknowledge these correlations.
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64 Five mutations were identified in more than five unrelated individuals: (1) p.E292V, (2) p.Y1515X, (3) IVS25-98 C .
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ABCA3 p.Tyr1515* 24871971:64:91
status: NEW69 All of the 19 Middle Eastern infants with the p.Y1515X/p.Y1515X genotype for whom complete clinical information was known presented with severe neonatal RDS and died before 3 months of age (Subjects 22-40; see Table E1; two infant outcomes unknown).
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ABCA3 p.Tyr1515* 24871971:69:48
status: NEWX
ABCA3 p.Tyr1515* 24871971:69:57
status: NEW[hide] Structural Features of the ATP-Binding Cassette (A... Int J Mol Sci. 2015 Aug 19;16(8):19631-44. doi: 10.3390/ijms160819631. Paolini A, Baldassarre A, Del Gaudio I, Masotti A
Structural Features of the ATP-Binding Cassette (ABC) Transporter ABCA3.
Int J Mol Sci. 2015 Aug 19;16(8):19631-44. doi: 10.3390/ijms160819631., [PMID:26295388]
Abstract [show]
In this review we reported and discussed the structural features of the ATP-Binding Cassette (ABC) transporter ABCA3 and how the use of bioinformatics tools could help researchers to obtain a reliable structural model of this important transporter. In fact, a model of ABCA3 is still lacking and no crystallographic structures (of the transporter or of its orthologues) are available. With the advent of next generation sequencing, many disease-causing mutations have been discovered and many more will be found in the future. In the last few years, ABCA3 mutations have been reported to have important pediatric implications. Thus, clinicians need a reliable structure to locate relevant mutations of this transporter and make genotype/phenotype correlations of patients affected by ABCA3-related diseases. In conclusion, we strongly believe that the model preliminarily generated by these novel bioinformatics tools could be the starting point to obtain more refined models of the ABCA3 transporter.
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111 In particular, we focused on the following mutations: p.E292V, p.E690K, p.R1333G, p.W1142X, p.Y1515X, and p.L1553P.
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ABCA3 p.Tyr1515* 26295388:111:94
status: NEW114 p.E690K reside in the NBD1, whereas p.Y1515X and p.L1553P are localized in the NBD2.
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ABCA3 p.Tyr1515* 26295388:114:38
status: NEW