{"id":12337,"date":"2026-03-12T16:00:15","date_gmt":"2026-03-12T16:00:15","guid":{"rendered":"http:\/\/sebigec.es\/blog\/?guid=44e6e506cbd9d11da1fbebe0fa4f6bfd"},"modified":"2026-03-12T16:00:15","modified_gmt":"2026-03-12T16:00:15","slug":"diagnosis-complexity-of-dentinogenesis-imperfecta-involving-dspp-genetic-variants","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2026\/03\/12\/diagnosis-complexity-of-dentinogenesis-imperfecta-involving-dspp-genetic-variants\/","title":{"rendered":"Diagnosis complexity of dentinogenesis imperfecta involving DSPP genetic variants"},"content":{"rendered":"<sec><st>Background<\/st><p>Variants in the dentin sialophosphoprotein (<I>DSPP<\/I>) gene are associated with dentin dysplasia type II (DD-II; OMIM # 125420) and dentinogenesis imperfecta (DI) types II (OMIM # 125490) and III (OMIM # 125500). <I>DSPP<\/I> encodes a precursor protein cleaved into three dentin matrix proteins: dentin sialoprotein (DSP), dentin phosphoprotein\/phosphophoryn (DPP) and dentin glycoprotein (DGP). Exon 5 contains over 200 tandem 9-base pair repeats (DSS domain), complicating sequencing with standard methods.<\/p><\/sec><sec><st>Materials and methods<\/st><p>We studied 112 individuals (42 index cases and 70 relatives) with clinical signs of DI or DD. DNA extracted from saliva was analysed using the GenoDENT next-generation sequencing panel. For inconclusive cases, long-range PCR and Oxford Nanopore Technology (ONT) long-read sequencing were used to overcome limitations in analysing the repetitive <I>DSPP<\/I> region.<\/p><\/sec><sec><st>Results<\/st><p>Pathogenic or likely pathogenic <I>DSPP<\/I> variants were identified in 41 families, including 8 known and 14 novel variants. Most were in exon 5, causing frameshifts resulting in a &ndash;1 reading-frame shift with a hydrophobic C-terminal extension and termination at a downstream stop codon. ONT sequencing enabled detection in cases where short-read methods failed. Several variants showed familial segregation and variable expressivity.<\/p><\/sec><sec><st>Conclusion<\/st><p>This study demonstrates the value of long-read sequencing to resolve complex <I>DSPP<\/I> regions and expands the variant spectrum. The variability in clinical presentation suggests the influence of modifier factors, warranting further genotype&ndash;phenotype studies.<\/p><\/sec>","protected":false},"excerpt":{"rendered":"<p>BackgroundVariants in the dentin sialophosphoprotein (DSPP) gene are associated with dentin dysplasia type II (DD-II; OMIM # 125420) and dentinogenesis imperfecta (DI) types II (OMIM # 125490) and III (OMIM # 125500). DSPP encodes a precursor protein c&#8230;<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,8,9],"tags":[],"class_list":["post-12337","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg-first","category-open-access"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/12337","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=12337"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/12337\/revisions"}],"predecessor-version":[{"id":12338,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/12337\/revisions\/12338"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=12337"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=12337"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=12337"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}