ABCA3 p.Lys914Arg
| Predicted by SNAP2: | A: D (59%), C: D (59%), D: D (53%), E: N (53%), F: D (63%), G: D (53%), H: N (57%), I: N (57%), L: N (53%), M: N (53%), N: N (66%), P: D (59%), Q: N (61%), R: N (82%), S: N (61%), T: N (72%), V: D (53%), W: D (80%), Y: D (59%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Inherited surfactant deficiency caused by uniparen... J Pediatr. 2009 Dec;155(6):854-859.e1. Epub 2009 Aug 3. Hamvas A, Nogee LM, Wegner DJ, Depass K, Christodoulou J, Bennetts B, McQuade LR, Gray PH, Deterding RR, Carroll TR, Kammesheidt A, Kasch LM, Kulkarni S, Cole FS
Inherited surfactant deficiency caused by uniparental disomy of rare mutations in the surfactant protein-B and ATP binding cassette, subfamily a, member 3 genes.
J Pediatr. 2009 Dec;155(6):854-859.e1. Epub 2009 Aug 3., [PMID:19647838]
Abstract [show]
OBJECTIVE: To characterize inheritance of homozygous, rare, recessive loss-of-function mutations in surfactant protein-B (SFTPB) or ATP binding cassette, subfamily A, member 3 (ABCA3) genes in newborns with lethal respiratory failure. STUDY DESIGN: We resequenced genes from parents whose infants were homozygous for mutations in SFTPB or ABCA3. For infants with only 1 heterozygous parent, we performed microsatellite analysis for chromosomes 2 (SFTPB) and 16 (ABCA3). RESULTS: We identified 1 infant homozygous for the g.1549C > GAA mutation (121ins2) in SFTPB for whom only the mother was heterozygous and 3 infants homozygous for mutations in ABCA3 (p.K914R, p.P147L, and c.806_7insGCT) for whom only the fathers were heterozygous. For the SP-B-deficient infant, microsatellite markers confirmed maternal heterodisomy with segmental isodisomy. Microsatellite analysis confirmed paternal isodisomy for the 3 ABCA3-deficient infants. Two ABCA3-deficient infants underwent lung transplantation at 3 and 5 months of age, respectively, and 2 infants died. None exhibited any nonpulmonary phenotype. CONCLUSIONS: Uniparental disomy should be suspected in infants with rare homozygous mutations in SFTPB or ABCA3. Confirmation of parental carrier status is important to provide recurrence risk and to monitor expression of other phenotypes that may emerge through reduction to homozygosity of recessive alleles.
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3 Results We identified 1 infant homozygous for the g.1549C > GAA mutation (121ins2) in SFTPB for whom only the mother was heterozygous and 3 infants homozygous for mutations in ABCA3 (p.K914R, p.P147L, and c.806_7insGCT) for whom only the fathers were heterozygous.
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ABCA3 p.Lys914Arg 19647838:3:185
status: NEW42 With electron microscopy, dense inclusions within the lamellar bodies were identified, as reported previously with ABCA3 deficiency.4,21 Sequence analysis of ABCA3 revealed a novel homozygous A>G transition in the second nucleotide of codon 914 (c.2741A>G) that changes lysine to arginine (p.K914R) and is predicted to be ''not tolerated`` by SIFT (http://blocks.fhcrc.org/sift/SIFT.html) and ''potentially damaging`` by Polyphen (http://genetics.bwh.harvard.edu/ pph/).
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ABCA3 p.Lys914Arg 19647838:42:292
status: NEW81 Informative variants in ABCA3 Variant ID Child Mother Father ABCA3 infant 1 rs323017 c.2514-93 A > G (Intron 19) G/G A/A A/G rs313908 c.2701-33 C > G (Intron 20) G/G C/C C/G Mutation c.2741A > G (p.K914R) G/G A/A A/G rs313909 c.3004 + 34 C > T (Intron 21) C/C T/T C/T rs1183064 c.3704-116 A > T (Intron 24) T/T A/A A/T ABCA3 infant 2 N/A c.-27 + 126 G > A (Intron 3) A/A G/G A/G Mutation c.440C > T (p.P147L) T/T C/C C/T rs170447 c.1741 + 33 G > A (Intron 14) A/A A/G A/G rs2240523 c.1742-116 C > T (Intron 14) C/C C/T C/T ABCA3 infant 3 Mutation c.806_807insGCT Ins/ins Normal/normal Ins/normal THE JOURNAL OF PEDIATRICS www.jpeds.com Vol. 155, No.
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ABCA3 p.Lys914Arg 19647838:81:198
status: NEW41 With electron microscopy, dense inclusions within the lamellar bodies were identified, as reported previously with ABCA3 deficiency.4,21 Sequence analysis of ABCA3 revealed a novel homozygous A>G transition in the second nucleotide of codon 914 (c.2741A>G) that changes lysine to arginine (p.K914R) and is predicted to be ''not tolerated`` by SIFT (http://blocks.fhcrc.org/sift/SIFT.html) and ''potentially damaging`` by Polyphen (http://genetics.bwh.harvard.edu/ pph/).
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ABCA3 p.Lys914Arg 19647838:41:292
status: NEW[hide] Interstitial lung disease in two brothers with nov... Eur J Pediatr. 2013 Jul;172(7):953-7. doi: 10.1007/s00431-013-1977-8. Epub 2013 Feb 27. Kitazawa H, Moriya K, Niizuma H, Kawano K, Saito-Nanjo Y, Uchiyama T, Rikiishi T, Sasahara Y, Sakamoto O, Setoguchi Y, Kure S
Interstitial lung disease in two brothers with novel compound heterozygous ABCA3 mutations.
Eur J Pediatr. 2013 Jul;172(7):953-7. doi: 10.1007/s00431-013-1977-8. Epub 2013 Feb 27., [PMID:23443156]
Abstract [show]
Mutations in genes critical for surfactant metabolism, including surfactant protein C (SP-C) and ABCA3, are well-recognized causes of interstitial lung disease. Recessive mutations in ABCA3 were first attributed to fatal respiratory failure in full-term neonates, but they are also increasingly being recognized as a cause of respiratory disorders with less severe phenotypes in older children and also adults. Here, we report a 20-month-old boy with interstitial lung disease caused by two distinct ABCA3 mutations. Initial treatment with methylprednisolone was unsuccessful, but the additional administration of hydroxychloroquine was effective. The family history revealed that the patient's older brother had died of idiopathic interstitial lung disease at 6 months of age, suggesting a genetic etiology of the disease. Sequence analyses of SP-C and ABCA3 genes were performed using DNA samples from the patient himself, his parents, and his brother. These analyses revealed novel compound heterozygous mutations in the coding exons of ABCA3 in both the patient and his brother: c.2741A > G, of paternal origin, and c.3715_3716insGGGGGG, of maternal origin. Conclusion Since ABCA3 mutations seem to be a heterogeneous entity with various phenotypes, we recommend genetic testing for mutations in SP-C and ABCA3 genes to be considered in children with unexplained interstitial lung disease.
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51 The patient`s father showed a single 218-bp band representing the wild-type allele, while the other family members showed 130- and 94-bp bands from the BmrI-digested mutant alleles, in addition to wild-type bands (using the primers in reference 20), demonstrating two different heterozygous mutations in the patient: an A to G substitution at c.2741 in exon 21 (c.2741A>G), which resulted in a lysine to arginine (p.K914R) substitution (Fig. 3a); and a 6 bp in-frame insertion in exon 25 (c.3715_3716insGGGGGG), which added two glycines to the protein product (p.L1238_E1239insGG) and created a new BmrI digestion site (Fig. 3b).
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ABCA3 p.Lys914Arg 23443156:51:417
status: NEW