ABCD1 p.Arg591Pro
| ClinVar: |
c.1771C>T
,
p.Arg591Trp
D
, Pathogenic
|
| Predicted by SNAP2: | A: D (91%), C: D (95%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), I: D (95%), K: D (91%), L: D (91%), M: D (91%), N: D (95%), P: D (95%), Q: D (95%), S: D (95%), T: D (95%), V: D (95%), W: D (95%), Y: D (95%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: D, P: D, Q: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] ABCD1 mutations and the X-linked adrenoleukodystro... Hum Mutat. 2001 Dec;18(6):499-515. Kemp S, Pujol A, Waterham HR, van Geel BM, Boehm CD, Raymond GV, Cutting GR, Wanders RJ, Moser HW
ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations.
Hum Mutat. 2001 Dec;18(6):499-515., [PMID:11748843]
Abstract [show]
X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene, which encodes a peroxisomal ABC half-transporter (ALDP) involved in the import of very long-chain fatty acids (VLCFA) into the peroxisome. The disease is characterized by a striking and unpredictable variation in phenotypic expression. Phenotypes include the rapidly progressive childhood cerebral form (CCALD), the milder adult form, adrenomyeloneuropathy (AMN), and variants without neurologic involvement. There is no apparent correlation between genotype and phenotype. In males, unambiguous diagnosis can be achieved by demonstration of elevated levels of VLCFA in plasma. In 15 to 20% of obligate heterozygotes, however, test results are false-negative. Therefore, mutation analysis is the only reliable method for the identification of heterozygotes. Since most X-ALD kindreds have a unique mutation, a great number of mutations have been identified in the ABCD1 gene in the last seven years. In order to catalog and facilitate the analysis of these mutations, we have established a mutation database for X-ALD ( http://www.x-ald.nl). In this review we report a detailed analysis of all 406 X-ALD mutations currently included in the database. Also, we present 47 novel mutations. In addition, we review the various X-ALD phenotypes, the different diagnostic tools, and the need for extended family screening for the identification of new patients.
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174 P560S 7 1678C>T n.d. # P560L 7 1679C>T Reduced P560L 7 1679C>T Reduced fs I588 7 1765delC n.d. # R591P 7 1772G>C Absent S606L 8 1817C>T Present E609K 8 1825G>A Absent E609K 8 1825G>A Absent R617C 8 1849C>T Absent R617H 8 1850G>A Absent R617H 8 1850G>A Absent A626T 9 1876G>A Absent A626T 9 1876G>A Absent A626D 9 1877C>A n.d. # E630G 9 1889A>G n.d. # C631Y 9 1892G>A n.d. # T632I 9 1895C>T n.d. # V635M 9 1903G>A n.d. # L654P 9 1961T>C Absent # R660W 9 1978C>T Absent fs L663 9 1988insT n.d. # fs L663 IVS 9 IVS9+1g>a n.d. # fs L663 IVS 9 IVS9-1g>a n.d. # H667D 10 1999C>G Absent # T668I 10 2003C>T Absent # T693M 10 2078C>T Present # exon1-5del 1-5 n.d. # The 47 mutations marked with a # are novel unique mutations reported for the first time in this paper.
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ABCD1 p.Arg591Pro 11748843:174:97
status: NEW[hide] Adrenoleukodystrophy in Norway: high rate of de no... Pediatr Neurol. 2013 Mar;48(3):212-9. doi: 10.1016/j.pediatrneurol.2012.12.007. Horn MA, Retterstol L, Abdelnoor M, Skjeldal OH, Tallaksen CM
Adrenoleukodystrophy in Norway: high rate of de novo mutations and age-dependent penetrance.
Pediatr Neurol. 2013 Mar;48(3):212-9. doi: 10.1016/j.pediatrneurol.2012.12.007., [PMID:23419472]
Abstract [show]
To investigate X-linked adrenoleukodystrophy in an unselected population, we performed a population based, cross-sectional prevalence study, supplemented by a retrospective study of deceased subjects. Sixty-three subjects (34 males, 29 females) belonging to 22 kindreds were included. Thirty-nine subjects (13 males, 26 females) were alive, and 24 (21 males, 3 females) were deceased on the prevalence day. The point prevalence of X-linked adrenoleukodystrophy in Norway on July 1, 2011, was 0.8 per 100,000 inhabitants. The incidence at birth in the period 1956-1995 was 1.6 per 100,000 inhabitants. An age-dependent penetrance was observed among males and females, with more severe phenotypes appearing with rising age. Only 5% of deceased males had not developed cerebral leukodystrophy. No female older than 50 years was neurologically intact. Sixteen mutations in the ABCD1 gene were identified. De novo mutations were found in 19% of probands. The frequency of X-linked adrenoleukodystrophy was lower in Norway than reported in the literature. A more severe natural course than previously reported was observed, indicating a need for better follow-up of both male and female patients. Given the high rate of de novo mutations, identification programs such as newborn screening may be required to offer timely treatment to all patients.
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145 ABCD1 gene mutations found in 21 Norwegian kindred with X-ALD* Gene Effect Amino Acid Effect Exon Reported n Kindred c.99C>A p.Y33X 1 No 1 c.139C>T p.Q47X 1 Yes 1 c.293C>A p.S98X 1 No 1 c.589_590delCT p.L197DfsX103 1 No 1 c.761C>T p.T254M 1 Yes 1 c.796G>A p.G266A 1 Yes 1 c.1202G>A p.R401Q 3 Yes 3 c.1390C>T p.R464X 4 Yes 2 c.1415_1416delAG p.Q472RfsX83 5 Yes 1 c.1497-1505del p.E499-H505delinsD 6 No 1 c.1553G>A p.R518Q 6 Yes 3 c.1581C>A p.Y527X 6 No 1 c.1585_1587delGGT p.G529del 6 Yes 1 c.1731delA p.A578PfsX58 7 No 1 c.1772G>C p.R591P 7 Yes 1 c.1822G>A p.G608S 8 Yes 1 Abbreviation: n &#bc; kindred sharing this mutation * One kindred was unavailable for genotyping. concerning the number of at-risk subjects and their health status was obtained.
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ABCD1 p.Arg591Pro 23419472:145:533
status: NEW