ABCA4 p.Thr1253Leu
| ClinVar: |
c.3759G>A
,
p.Thr1253=
N
, Benign
c.3758C>T , p.Thr1253Met ? , not provided |
| Predicted by SNAP2: | A: N (78%), C: N (72%), D: N (72%), E: N (78%), F: N (57%), G: N (72%), H: N (87%), I: N (72%), K: N (82%), L: N (66%), M: N (72%), N: N (87%), P: N (66%), Q: N (78%), R: N (78%), S: N (93%), V: N (78%), W: D (66%), Y: N (61%), |
| Predicted by PROVEAN: | A: N, C: D, D: N, E: N, F: D, G: D, H: N, I: D, K: N, L: D, M: N, N: N, P: D, Q: N, R: N, S: N, V: D, W: D, Y: D, |
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[hide] Spectrum of ABCA4 (ABCR) gene mutations in Spanish... Hum Mutat. 2001 Jun;17(6):504-10. Paloma E, Martinez-Mir A, Vilageliu L, Gonzalez-Duarte R, Balcells S
Spectrum of ABCA4 (ABCR) gene mutations in Spanish patients with autosomal recessive macular dystrophies.
Hum Mutat. 2001 Jun;17(6):504-10., [PMID:11385708]
Abstract [show]
The ABCA4 gene has been involved in several forms of inherited macular dystrophy. In order to further characterize the complex genotype-phenotype relationships involving this gene, we have performed a mutation analysis of ABCA4 in 14 Spanish patients comprising eight STGD (Stargardt), four FFM (fundus flavimaculatus), and two CRD (Cone-rod dystrophy) patients. SSCP (single-strand conformation polymorphism) analysis and DNA sequencing of the coding and 5' upstream regions of this gene allowed the identification of 16 putatively pathogenic alterations, nine of which are novel. Most of these were missense changes, and no patient was found to carry two null alleles. Overall, the new data agree with a working model relating the different pathogenic phenotypes to the severity of the mutations. When considering the information presented here together with that of previous reports, a picture of the geographic distribution of three particular mutations emerges. The R212C change has been found in French, Italian, Dutch, German, and Spanish but not in British patients. In the Spanish collection, R212C was found in a CRD patient, indicating that it may be a rather severe change. In contrast, c.2588G>C, a very common mild allele in the Dutch population, is rarely found in Southern Europe. Interestingly, the c.2588G>C mutation has been found in a double mutant allele together with the missense R1055W. Finally, the newly described L1940P was found in two unrelated Spanish patients, and may be a moderate to severe allele.
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No. Sentence Comment
41 Mutations L686S, c.2888delG, T1253L, c.4253 +5G>A, N1799D, N1805D, L1940P , and L2060R were confirmed by TaqI, Sau96I, HgaI, HhaI, MboI, TaqI, HaeIII, and MspI digestion, respectively.
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ABCA4 p.Thr1253Leu 11385708:41:29
status: NEW59 Pathogenic Mutations In the absence of a functional assay, it is difficult to relate the structural alteration with the TABLE 1. Summary of the Pathogenic Variants Found in the Screening of the ABCA4 Gene Family (NAS) Paternal allele (E) Maternal allele (E) Onset (years) Phenotype SB1 c.3211-3212insGT (22) R212C (6) 9 CRD M266 (2) c.4253+5G>A (28) L2060R (46) 7/4 CRD SM3 [R152Q (5); R2107H (46)] [R152Q (5); R2107H (46)] 7 STGD SZ2 L1940P (41) ND 8 STGD SM1 N1799D (38) ND 9 STGD SM2 c.2888delG (19) [R1055W (21); C.2588G>C (17)] 11 STGD SP1 ND ND 12 STGD SZ3 ND ND 12 STGD M280 N1805D (39) N1805D (39) 14 STGD SB2 (2) R1108C (22) L686S (14) 18/11 STGD SZ4 ND ND 20/28 FFM SP2 ND ND 21 FFM SM4 [T1253L (25); G1961E (42)] ND 38 FFM SZ1 L1940P (41) ND 28 FFM Novel putative pathogenic variants are depicted in bold type and their corresponding nucleotide changes are as follows: L686S=c.2057T>C; R1055W=c.3163C>T; T1253L=c.3758C>T; N1799D=c.5396A>G; N1805D=c.5413A>G; L1940P=c.5819T>C; L2060R=c.6179T>G.
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ABCA4 p.Thr1253Leu 11385708:59:698
status: NEW72 The fact that the more conservative changes R152Q and T1253L were found in a double mutant allele makes it difficult to evaluate their contribution to the disease phenotype.
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ABCA4 p.Thr1253Leu 11385708:72:54
status: NEW