NM_058172.6(ANTXR2):c.1073dup (p.Ala359fs) AND Hyaline fibromatosis syndrome

Significance: Pathogenic
ClinVar: RCV000002722

Variant: NM_058172.6(ANTXR2):c.1073dup (p.Ala359fs)

Type: Variant
Allele: NM_058172.6(ANTXR2):c.1073dup (p.Ala359fs) 17643
Type: Duplication
Location: Chr4: 80905986 - assembly GRCh37
Chr4: 79984832 - assembly GRCh38
References: dbSNP: 312262690
OMIM: 608041.0007
Undiagnosed Diseases Network,NIH: 4338e405-4459-4234-9076-32d3a58ac2c7_1


Disease: Hyaline fibromatosis syndrome


    In a Hispanic individual living in the United States, Hanks et al. (2003) found that infantile-onset hyaline fibromatosis syndrome (228600) was related to homozygosity for insertion of a cytosine in the poly(C) tract in exon 13 of the CMG2 gene. In 2 other families, each with 1 affected individual (1 of Puerto Rican/African American origin and 1 of Chinese origin), Hanks et al. (2003) identified the 1601insC frameshift mutation in heterozygous state; the other allele was not characterized in these cases. The mutation appeared to have arisen independently in these 3 families, because they carried different 4q21 haplotypes and CMG2 polymorphisms. Moreover, 2 further families had different mutations involving the poly(C) tract, which appears to be a mutation hotspot, presumably owing to the repetitive sequence.
    Denadai et al. (2012) noted that Hanks et al. (2003) did not number their mutations using the A of the ATG start codon of their ANTXR2 sequence (GenBank AK091721) as nucleotide 1. The correct numbering of this mutation, using the A of the ATG start codon of the ANTXR2 reference sequence (GenBank NM_058172.5) as nucleotide 1, is 1073insC.
PMID:14508707, PMID:22383261