ABCD1 p.Ala616Asp
| Predicted by SNAP2: | C: D (80%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), I: D (95%), K: D (95%), L: D (95%), M: D (95%), N: D (95%), P: D (95%), Q: D (95%), R: D (95%), S: D (91%), T: D (80%), V: D (95%), W: D (95%), Y: D (95%), |
| Predicted by PROVEAN: | C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: N, T: D, V: D, W: D, Y: D, |
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[hide] Efferent and afferent evoked potentials in patient... Clin Neurol Neurosurg. 2010 Feb;112(2):131-6. Epub 2009 Dec 5. Matsumoto H, Hanajima R, Terao Y, Hamada M, Yugeta A, Shirota Y, Yuasa K, Sato F, Matsukawa T, Takahashi Y, Goto J, Tsuji S, Ugawa Y
Efferent and afferent evoked potentials in patients with adrenomyeloneuropathy.
Clin Neurol Neurosurg. 2010 Feb;112(2):131-6. Epub 2009 Dec 5., [PMID:19963315]
Abstract [show]
OBJECTIVE: This paper investigates efferent and afferent conductions of the central nervous system by various evoked potentials in patients with adrenomyeloneuropathy (AMN). PATIENTS AND METHODS: Ten pure AMN patients without cerebral involvement were studied. Motor evoked potentials (MEPs), somatosensory evoked potentials (SEPs), auditory brainstem response (ABR), and pattern reversal full-field visual evoked potentials (VEPs) were recorded. For MEP recording, single-pulse or double-pulse magnetic brainstem stimulation (BST) was also performed. RESULTS: Abnormal MEP was observed in all ten patients, abnormal SEP in all ten, abnormal ABR in nine, and abnormal VEP in only one. Brainstem latency was measured in three of the seven patients with central motor conduction time (CMCT) prolongation. The cortical-brainstem conduction time was severely prolonged along the normal or mildly delayed brainstem-cervical conduction time in those three patients. CONCLUSIONS: The pattern of normal VEP and abnormal MEP, SEP, ABR is a clinically useful electrophysiological feature for the diagnosis. BST techniques are helpful to detect, functionally, intracranial corticospinal tract involvement, probably demyelination, in pure AMN patients.
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35 Case Age ABCD1 mutation Disease duration (years) Main symptom(s) Brain MRI Loes score Spinal MRI 1 32 Missense (H667N) 1 Spastic gait, pigmentation Normal 0 Normal 2 44 Nonsense (W595X) 1 Spastic gait, sensory disturbance (leg) Normal 0 Atrophy 3 61 N.E. 4 Spastic gait, muscular weakness (leg), sensory disturbance (leg) Normal 0 Normal 4 30 Missense (S290W) 5 Spastic gait, sensory disturbance (leg), dysuria, dyschezia, impotence P, V 2.5 Normal 5 31 Missense (F540S) 5 Spastic gait V 0.5 Normal 6 24 Missense (A616D) 6 Spastic gait, sensory disturbance (leg), dysuria, impotence Normal 0 Normal 7 31 Frameshift (Y281) 8 Spastic gait, sensory disturbance (leg), dyschezia C 0.5 Normal 8 33 Missense (G277R) 8 Spastic gait, dysuria, dyschezia impotence P 2 Atrophy 9 58 N.E. 18 Spastic gait, dysuria Normal 0 Atrophy 10 58 N.E. 19 Spastic gait, impotence Normal 0 Normal MRI: magnetic resonance image, P: pyramidal system, V: visual pathway, C: cerebellum, N.E.: not examined.
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ABCD1 p.Ala616Asp 19963315:35:514
status: NEW33 Case Age ABCD1 mutation Disease duration (years) Main symptom(s) Brain MRI Loes score Spinal MRI 1 32 Missense (H667N) 1 Spastic gait, pigmentation Normal 0 Normal 2 44 Nonsense (W595X) 1 Spastic gait, sensory disturbance (leg) Normal 0 Atrophy 3 61 N.E. 4 Spastic gait, muscular weakness (leg), sensory disturbance (leg) Normal 0 Normal 4 30 Missense (S290W) 5 Spastic gait, sensory disturbance (leg), dysuria, dyschezia, impotence P, V 2.5 Normal 5 31 Missense (F540S) 5 Spastic gait V 0.5 Normal 6 24 Missense (A616D) 6 Spastic gait, sensory disturbance (leg), dysuria, impotence Normal 0 Normal 7 31 Frameshift (Y281) 8 Spastic gait, sensory disturbance (leg), dyschezia C 0.5 Normal 8 33 Missense (G277R) 8 Spastic gait, dysuria, dyschezia impotence P 2 Atrophy 9 58 N.E. 18 Spastic gait, dysuria Normal 0 Atrophy 10 58 N.E. 19 Spastic gait, impotence Normal 0 Normal MRI: magnetic resonance image, P: pyramidal system, V: visual pathway, C: cerebellum, N.E.: not examined.
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ABCD1 p.Ala616Asp 19963315:33:514
status: NEW[hide] Identification of novel SNPs of ABCD1, ABCD2, ABCD... Neurogenetics. 2011 Feb;12(1):41-50. Epub 2010 Jul 27. Matsukawa T, Asheuer M, Takahashi Y, Goto J, Suzuki Y, Shimozawa N, Takano H, Onodera O, Nishizawa M, Aubourg P, Tsuji S
Identification of novel SNPs of ABCD1, ABCD2, ABCD3, and ABCD4 genes in patients with X-linked adrenoleukodystrophy (ALD) based on comprehensive resequencing and association studies with ALD phenotypes.
Neurogenetics. 2011 Feb;12(1):41-50. Epub 2010 Jul 27., [PMID:20661612]
Abstract [show]
Adrenoleukodystrophy (ALD) is an X-linked disorder affecting primarily the white matter of the central nervous system occasionally accompanied by adrenal insufficiency. Despite the discovery of the causative gene, ABCD1, no clear genotype-phenotype correlations have been established. Association studies based on single nucleotide polymorphisms (SNPs) identified by comprehensive resequencing of genes related to ABCD1 may reveal genes modifying ALD phenotypes. We analyzed 40 Japanese patients with ALD. ABCD1 and ABCD2 were analyzed using a newly developed microarray-based resequencing system. ABCD3 and ABCD4 were analyzed by direct nucleotide sequence analysis. Replication studies were conducted on an independent French ALD cohort with extreme phenotypes. All the mutations of ABCD1 were identified, and there was no correlation between the genotypes and phenotypes of ALD. SNPs identified by the comprehensive resequencing of ABCD2, ABCD3, and ABCD4 were used for association studies. There were no significant associations between these SNPs and ALD phenotypes, except for the five SNPs of ABCD4, which are in complete disequilibrium in the Japanese population. These five SNPs were significantly less frequently represented in patients with adrenomyeloneuropathy (AMN) than in controls in the Japanese population (p=0.0468), whereas there were no significant differences in patients with childhood cerebral ALD (CCALD). The replication study employing these five SNPs on an independent French ALD cohort, however, showed no significant associations with CCALD or pure AMN. This study showed that ABCD2, ABCD3, and ABCD4 are less likely the disease-modifying genes, necessitating further studies to identify genes modifying ALD phenotypes.
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84 Interestingly, the five previously described SNPs (rs17782508, rs2301345, rs4148077, rs4148078, and rs3742801) that are in complete linkage disequilibrium were significantly less frequently represented in the patients with Japanese AMN than in the controls in the Japanese population (p=0.0468), whereas Table 2 Identified ABCD1 mutations: mutations of ABCD1 that result in amino acid substitutions or in-frame deletions Patient number Phenotype Mutation of ABCD1 Effect of mutation of ABCD1 Position of mutation 13 CCALD 709C>T S108L Loop1 14 CCALD 709C>T S108L Loop1 15 CCALD 829A>G N148S TM2 16 CCALD 1026A>G N214D TM3 17 CCALD 1182G>A G266R Between TM4 and EAA-like 18 CCALD 1324T>Ca L313P Between EAA-like and TM5 19 CCALD 1938C>T R518W Walker A 20 CCALD 1939G>A R518Q Walker A 21 CCALD 2017A>G Q544R Between Walker A and Cons 22 CCALD 2017A>G Q544R Between Walker A and Cons 23 CCALD 2065C>T P560L Between Walker A and Cons 24 CCALD 2065C>T P560L Between Walker A and Cons 25 CCALD Del. 2145-2156 Del. HILQ587-590 Between Walker A and Cons 26 AdultCer Del. 1257-1259 Del.E291 EAA-like 27 AdultCer 2005T>C F540S Between Walker A and Cons 28 AdultCer 2358C>T R660W C-terminal to Walker B 29 AdultCer 2385C>A H667N C-terminal to Walker B 30 AMN-Cer 1146A>C T254P TM4 31 AMN 636C>T P84S TM1 32 AMN 709C>T S108L Loop1 33 AMN 1182G>A G266R Between TM4 and EAA-like 34 AMN 1197G>A E271K Between TM4 and EAA-like 35 AMN 1215G>Aa G277R Between TM4 and EAA-like 36 AMN 1255C>G S290W EAA-like 37 AMN 1581C>T R401W Between TM6 and Walker A 38 AMN 2233C>A A616D Cons 39 AMN 2385C>A H667N C-terminal to Walker B 40 Asymptomatic 2211G>A E609K Cons Amino acid residue numbers in ALDP are based on Mosser et al. [1].
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ABCD1 p.Ala616Asp 20661612:84:1549
status: NEW