Mutations in ROGDI Cause Kohlschütter-Tönz Syndrome

Schossig, Anna; Wolf, Nicole I.; Fischer, Christine; Fischer, Maria; Stocker, Gernot; Pabinger, Stephan; Dander, Andreas; Steiner, Bernhard; Tönz, O; Kotzot, Dieter; Haberlandt, Edda; Amberger, Albert; Burwinkel, Barbara; Wimmer, Katharina; Fauth, Christine; Grond‐Ginsbach, Caspar; Koch, Martin Jean; Deichmann, Annette; Kalle, Christof von; Bartram, Claus R.; Kohlschütter, Alfried; Trajanoski, Zlatko; Zschocke, Johannes

doi:10.1016/j.ajhg.2012.02.012

Cited by 63 publications

(84 citation statements)

References 19 publications

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“…Other mutations described in the literature ( fig. 1 ) include deletions, duplications, splicing, and frameshift mutations and are scattered in exons 4-7 and introns 1 and 7 [Schossig et al, 2012a;Mory et al, 2012;Tucci et al, 2013].…”

Section: Discussionmentioning

confidence: 99%

A Novel Mutation in the ROGDI Gene in a Patient with Kohlschütter-Tönz Syndrome

Huckert¹,

Mecili²,

Laugel-Haushalter

et al. 2014

Mol Syndromol

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Kohlschütter-Tönz Syndrome (KTZS) is an autosomal recessive disorder caused by mutations in the ROGDI gene. This syndrome is characterized by epilepsy, psychomotor regression and amelogenesis imperfecta. In this paper, we report a case of a 13-year-old Malian girl presenting with this rare disease. By genetic analysis, we identified a novel ROGDI homozygous mutation NM_024589.1: c.117+1G>T [Chr16 (GRCh37): g.4852382C>A] which confirmed the diagnosis of Kohlschütter-Tönz syndrome. The mutation abolishes the usual splice donor site of intron 2 which leads to the deletion of exon 2 and in-frame assembly of exon 3. Exon 2 encodes a highly conserved leucine-rich region that is essential for ROGDI protein function. Hence, this deletion may affect the function of the ROGDI protein.

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Section: Discussionmentioning

confidence: 99%

A Novel Mutation in the ROGDI Gene in a Patient with Kohlschütter-Tönz Syndrome

Huckert¹,

Mecili²,

Laugel-Haushalter

et al. 2014

Mol Syndromol

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“…These 2 conditions are listed separately on OMIM but appear to be the same entity. In some conditions, such as KolschuttersTonz syndrome (OMIM 226750, gene ROGDI), the enamel phenotype appears quite similar to the hypomineralized forms of amelogenesis imperfecta (Schossig et al 2012). The pathologic mechanism of this neurologic condition and function of the ROGDI gene product remain unknown, but one could speculate that the causative gene is expressed by ameloblasts and that its protein plays a critical role in enamel biomineralization.…”

Section: Discussionmentioning

confidence: 99%

The Molecular Basis of Hereditary Enamel Defects in Humans

2014

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The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel.

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“…As for teeth disease, amelogenesis imperfecta, characterized by abnormal enamel formation, and the related Kohlschütter-Tönz syndrome are examples of WES studied teeth diseases. Mutation in the FAM20A gene related with amelogenesis imperfecta (45) and the ROGDI gene mutation related with Kohlschütter-Tönz syndrome were found (46). One of successful examples for WES applying to the skin diseases is peeling skin syndrome, genetic disorder characterized by continual peeling of the skin.…”

Section: Discussionmentioning

confidence: 99%

“…That includes skeletal dysplasia, 3-M syndrome, osteogenesis imperfecta, chondrodysplasia and abnormal joint development, Miller syndrome -bone dis eases; amelogenesis imperfecta, Kohlschütter-Tönz syndrome -teeth diseases; as well as skin diseases -peeling skin syndrome, Kaposi's sarcoma (11,(41)(42)(43)(44)(45)(46)(47)(48). Skeletal dysplasia, that commonly is called dwarfism, is a group of disorders characterized by abnormalities of cartilage and bone growth.…”

Section: Discussionmentioning

confidence: 99%

Next-generation whole-exome sequencing contribution to identification of rare autosomal recessive diseases

Rančelis

Kučinskas²

2013

AML

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A rare disease is any disease that affects a small percentage of the population. In the European Union a disease is defined as rare if it affects less than 1 in 2,000 people. Despite a small percentage of affected people by one disease, the total number of rare diseases is estimated to be around 7,000–8,000, thus, because of their large number they have an impact on many people and even 30 million of European Union citizens may be suffering from them. Research of rare diseases may help to explain their mechanism or to develop more advanced diagnostics. Classical strategies for studies of rare autosomal recessive diseases encounter with additional problems (multiple genetic variants, de novo mutations, extremely rare cases) that make these strategies not enough effective. Next generation whole-exome sequencing (WES) opened a new page in Mendelian disease gene discovery – enabling to study autosomal recessive diseases in a new way. During 3 years of WES usage many novel mutations of autosomal recessive disease genes were discovered.

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Mutations in ROGDI Cause Kohlschütter-Tönz Syndrome

Cited by 63 publications

References 19 publications

A Novel Mutation in the <b><i>ROGDI</i></b> Gene in a Patient with Kohlschütter-Tönz Syndrome

A Novel Mutation in the <b><i>ROGDI</i></b> Gene in a Patient with Kohlschütter-Tönz Syndrome

The Molecular Basis of Hereditary Enamel Defects in Humans

Next-generation whole-exome sequencing contribution to identification of rare autosomal recessive diseases

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