EXT1

• Haploinsufficiency score: 3
• Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
• Haploinsufficiency Phenotype: EXOSTOSES, MULTIPLE, TYPE I

Evidence for haploinsufficiency phenotype

PubMed ID	Description
29529714	In 2018, Santos et al. used Sanger sequencing and Multiplex ligation-dependent probe amplification (MLPA) on 153 Brazilian patients in 114 families with multiple osteochondromas (MO) to identify variants in EXT1 and EXT2. The authors identified variants in EXT1 in 42 of the 114 unrelated individuals with MO. 33 of these variants were unique. Of these, 13 were frameshifts, 5 were missense variants, 11 were nonsense, 2 were splice site variants, and 2 were large deletions.
30334991	In 2018, Li et al. used Sanger sequencing and Multiplex ligation-dependent probe amplification (MLPA) on unrelated individuals from 73 Chinese families with hereditary multiple osteochondroma (HMO) to identify variants in EXT1 and EXT2. Analysis identified 33 unique variants in EXT1 in 39 families. Of these, 16 were frameshifts, 3 were nonsense variants, 5 were splice site variants, 4 were large deletions, and 1 was an in-frame deletion.
28690282	In 2017, Guo et al. used targeted next-generation sequencing (t-NGS) and Sanger sequencing on 10 patients with multiple osteochondromas (MO) to identify potential variants in EXT1 and EXT2. The authors identified 5 variants in EXT1, 3 of which were nonsense variants.

Haploinsufficiency phenotype comments:

Please see GeneReviews for a detailed discussion of the evidence supporting haploinsufficiency for EXT1. Per GeneReviews, "Osteochondromas were previously called exostoses; however, the term exostosis is no longer used to describe the lesions in HMO because the term osteochondroma specifies that these lesions are cartilaginous processes that ossify and not simply outgrowths of bone. The changed terminology has been adopted by the World Health Organization (WHO)."

• Triplosensitivity score: 0
• Strength of Evidence (disclaimer): No evidence for dosage pathogenicity