ABCG5 p.Gln16*
| ClinVar: |
c.46C>T
,
p.Gln16*
D
, Pathogenic
|
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[hide] Identification by whole-genome resequencing of gen... Hum Mol Genet. 2010 Nov 15;19(22):4313-8. Epub 2010 Aug 18. Rios J, Stein E, Shendure J, Hobbs HH, Cohen JC
Identification by whole-genome resequencing of gene defect responsible for severe hypercholesterolemia.
Hum Mol Genet. 2010 Nov 15;19(22):4313-8. Epub 2010 Aug 18., 2010-11-15 [PMID:20719861]
Abstract [show]
Whole-genome sequencing is a potentially powerful tool for the diagnosis of genetic diseases. Here, we used sequencing-by-ligation to sequence the genome of an 11-month-old breast-fed girl with xanthomas and very high plasma cholesterol levels (1023 mg/dl). Her parents had normal plasma cholesterol levels and reported no family history of hypercholesterolemia, suggesting either an autosomal recessive disorder or a de novo mutation. Known genetic causes of severe hypercholesterolemia were ruled out by sequencing the responsible genes (LDLRAP, LDLR, PCSK9, APOE and APOB), and sitosterolemia was ruled out by documenting a normal plasma sitosterol:cholesterol ratio. Sequencing revealed 3 797 207 deviations from the reference sequence, of which 9726 were nonsynonymous single-nucleotide substitutions. A total of 9027 of the nonsynonymous substitutions were present in dbSNP or in 21 additional individuals from whom complete exonic sequences were available. The 699 novel nonsynonymous substitutions were distributed among 604 genes, 23 of which were single-copy genes that each contained 2 nonsynonymous substitutions consistent with an autosomal recessive model. One gene, ABCG5, had two nonsense mutations (Q16X and R446X). This finding indicated that the infant has sitosterolemia. Thus, whole-genome sequencing led to the diagnosis of a known disease with an atypical presentation. Diagnosis was confirmed by the finding of severe sitosterolemia in a blood sample obtained after the infant had been weaned. These findings demonstrate that whole-genome (or exome) sequencing can be a valuable aid to diagnose genetic diseases, even in individual patients.
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No. Sentence Comment
7 One gene, ABCG5, had two nonsense mutations (Q16X and R446X).
X
ABCG5 p.Gln16* 20719861:7:45
status: VERIFIED65 A single gene, ABCG5, contained two different nonsense mutations: Q16X and R446X (Fig. 2B).
X
ABCG5 p.Gln16* 20719861:65:66
status: VERIFIED66 Sanger sequencing confirmed both mutations in the proband and that her mother and father were heterozygotes for the Q16X and R446X mutations, respectively (data not shown).
X
ABCG5 p.Gln16* 20719861:66:116
status: VERIFIED68 The ABCG5-R446X mutation was observed in a 10-year-old girl with sitosterolemia (21), whereas the Q16X mutation has not been reported previously.
X
ABCG5 p.Gln16* 20719861:68:98
status: VERIFIED