ABCMdb

ABCD1 p.Glu376Gln

Predicted by SNAP2:	A: N (61%), C: D (66%), D: N (82%), F: D (71%), G: N (57%), H: N (53%), I: N (53%), K: N (53%), L: N (53%), M: N (57%), N: N (61%), P: D (66%), Q: N (66%), R: D (59%), S: N (61%), T: N (61%), V: N (53%), W: D (85%), Y: D (75%),
Predicted by PROVEAN:	A: N, C: D, D: N, F: D, G: N, H: N, I: D, K: N, L: D, M: D, N: N, P: D, Q: N, R: N, S: N, T: N, V: D, W: D, Y: D,

[switch to compact view]
Comments [show]

None has been submitted yet.

Publications
[hide] Exome sequencing identifies mutations in ABCD1 and... BMC Med Genet. 2014 Sep 19;15:105. doi: 10.1186/s12881-014-0105-6. Zhang Y, Liu Y, Li Y, Duan Y, Zhang K, Wang J, Dai Y
Exome sequencing identifies mutations in ABCD1 and DACH2 in two brothers with a distinct phenotype.
BMC Med Genet. 2014 Sep 19;15:105. doi: 10.1186/s12881-014-0105-6., [PMID:25234129]

Abstract [show]
BACKGROUND: We report on two brothers with a distinct syndromic phenotype and explore the potential pathogenic cause. METHODS: Cytogenetic tests and exome sequencing were performed on the two brothers and their parents. Variants detected by exome sequencing were validated by Sanger sequencing. RESULTS: The main phenotype of the two brothers included congenital language disorder, growth retardation, intellectual disability, difficulty in standing and walking, and urinary and fecal incontinence. To the best of our knowledge, no similar phenotype has been reported previously. No abnormalities were detected by G-banding chromosome analysis or array comparative genomic hybridization. However, exome sequencing revealed novel mutations in the ATP-binding cassette, sub-family D member 1 (ABCD1) and Dachshund homolog 2 (DACH2) genes in both brothers. The ABCD1 mutation was a missense mutation c.1126G > C in exon 3 leading to a p.E376Q substitution. The DACH2 mutation was also a missense mutation c.1069A > T in exon 6, leading to a p.S357C substitution. The mother was an asymptomatic heterozygous carrier. Plasma levels of very-long-chain fatty acids were increased in both brothers, suggesting a diagnosis of adrenoleukodystrophy (ALD); however, their phenotype was not compatible with any reported forms of ALD. DACH2 plays an important role in the regulation of brain and limb development, suggesting that this mutation may be involved in the phenotype of the two brothers. CONCLUSION: The distinct phenotype demonstrated by these two brothers might represent a new form of ALD or a new syndrome. The combination of mutations in ABCD1 and DACH2 provides a plausible mechanism for this phenotype.

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
5 The ABCD1 mutation was a missense mutation c.1126G > C in exon 3 leading to a p.E376Q substitution. Login to comment
104 The ABCD1 mutation was a missense mutation c.1126G > C in exon 3, leading to a p. E376Q substitution (Figure 6), and the DACH2 mutation was also a missense mutation c.1069A > Tc.1069A > T in exon 6, leading to ap.S357C substitution (Figure 7). Login to comment
108 nlm.nih.gov/Blast.cgi) indicated that both the mutations, c.1126G > C transition (E376Q) of ABCD1 and c.1069A > T transition (p.S357C) of DACH2, occurred in highly conserved positions (Figure 6, 7). Login to comment
110 The variant c.1126G > C transition (E376Q) of ABCD1 was considered likely to be functionally benign, while the variant c.1069A > T transition (p.S357C) of DACH2 was likely to be functionally damaging. Login to comment
118 The ABCD1 mutation was a novel missense mutation, c.1126G > C transition (E376Q), in exon 3. Login to comment
132 E376Q missense mutation was at a highly conserved position in ABCD1 shown by comparison to the corresponding sequence of six vertebrates (lower panel). Login to comment
148 Although PolyPhen-2 predicted that the biophysical consequences of the variant c.1126G > C (E376Q) of ABCD1 were likely to be functionally benign, other variants in the same exon, such as c.1114A > T (p. K372*) and c.1137C > G (p.S379R), have been reported to lead to ALD [15]. Login to comment