A Novel Pathogenic Large Duplication in EXT1 Identified in a Family with Multiple Osteochondromas

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2024 Sep 28

PMID 39336760

Authors

Isabella Bartolotti

Klaudia Sobul

Serena Corsini

Davide Scognamiglio

Alice Moroni

Maria Gnoli

Luca Sangiorgi

Elena Pedrini

Affiliations

Soon will be listed here.

Abstract

Multiple osteochondromas (MO) is an autosomal dominant disorder and the most common genetic skeletal dysplasia, characterized by the growth of bone outgrowths capped by cartilage, called osteochondromas. Most MO cases are caused by mutations in the exostosin-1 () and exostosin-2 () genes. Only 5% of MO-causative variants are represented by single or multiple exon deletions; to date, no pathogenic large duplication has been described in the literature. In the present study, we describe the novel in-tandem intragenic duplication c.(1128_1202)_(1284+29_1344)dup involving exon 4 of (NM_000127.2), detected in a three-generation family with MO. The variant has been detected by MLPA (multiplex ligation-dependent probe amplification) and then confirmed with qPCR (quantitative PCR). Our finding expands the spectrum of MO-causing variants describing a pathogenic large duplication, underlying the importance of quantitative analysis in patients with negative sequencing.

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