medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLCmedgen-327Research ArticleКЛИНИЧЕСКИЕ СЛУЧАИCLINICAL CASEКлинико-молекулярно-генетические характеристики глазо-зубо-пальцевого синдромаClinical and molecular characteristics of oculodentodigital dysplasiaРуденскаяГ. Е.RudenskayaG. E.rudenskaya@med-gen.ruБлизнецЕ. А.BliznetzE. A.noemail@neicon.ruДеминаН. А.DyominaN. A.noemail@neicon.ruХлебниковаО. В.KhlebnikovaO. V.noemail@neicon.ruДадалиЕ. Л.DadalyE. L.noemail@neicon.ruПоляковА. В.PolyakovA. V.noemail@neicon.ruФГБНУ «Медико-генетический научный центр»РоссияResearch Centre for Medical GeneticsRussian Federation2017200220181693747Copyright © Руденская Г.Е., Близнец Е.А., Демина Н.А., Хлебникова О.В., Дадали Е.Л., Поляков А.В., 20182018Руденская Г.Е., Близнец Е.А., Демина Н.А., Хлебникова О.В., Дадали Е.Л., Поляков А.В.Rudenskaya G.E., Bliznetz E.A., Dyomina N.A., Khlebnikova O.V., Dadaly E.L., Polyakov A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/327

Глазо-зубо-пальцевой синдром (ГЗПС; oculodentodigital dysplasia) - аутосомно-доминантная болезнь, обусловленная мутациями гена коннексина 43 GJA1 . Типичная картина включает синдактилию кистей III типа (ульнарную), иногда в сочетании с синдактилией стоп, аномалии глаз, зубов, волос, носа. У трети больных в разном возрасте присоединяются неврологические симптомы: прогрессирующий спастический парапарез, расстройства тазовых функций, атаксия, очаговое поражение белого вещества при МРТ. Мутации гена GJA1 разнообразны. Около половины случаев ГЗПС обусловлены мутациями de novo . Представлены первые молекулярно верифицированные российские наблюдения ГЗПС: 4 неродственные семьи с 5 больными женщинами 10-59 лет. У всех имелись типичные аномалии развития и неврологические расстройства c меж- и внутрисемейными различиями. В трех семьях предварительными диагнозами были наследственные нейродегенерации, лишь у одной больной ГЗПС был клинически диагностирован в раннем возрасте. В экзоне 2 гена GJA1 найдены три не описанные ранее мутации в гетерозиготном состоянии: c.400_402delAAG (в двух семьях), с.461C>T (p.Thr154Ile) и с.94T>G (p.Phe32Val). В 3 несемейных случаях возникновение мутаций de novo доказано анализом ДНК родителей больных; в семье с больными матерью и дочерью мутация у матери, чьи родители здоровы, тоже, очевидно, возникла de novo .

Oculodentodigital dysplasia (ODDD) is autosomal dominant disorder caused by mutations in connexin 43 gene caused by heterozygous mutation in the connexin-43 gene (GJA1 caused by heterozygous mutation in the connexin-43 gene (GJA1 caused by heterozygous mutation in the connexin-43 gene (GJA1caused by heterozygous mutation in the connexin-43 gene (GJA1GJA1. Typical features are syndactyly IV-V or III-V fingers with or without feet syndactyly, anomalies of eyes, teeth, nose and hair. In about 30% of patients neurological disorders appear later in life: progressive spastic paraparesis (most common), neurogenic bladder/bowel, ataxia, white matter lesions on MRI. GJA1 mutations are numerous with no common, about 50% of cases are produced by mutations de novo. First Russian DNA-confirmed ODDD cases are presented: 4 unrelated families with 5 affected women age 10-59 yrs. All patients had typical anomalies and neurological symptoms with some inter- and intrafamilial differences. In three cases ODDD was not recognized earlier, preliminary diagnoses were hereditary neurodegenerations, only in 17-year-old patient ODDD was clinically diagnosed in early age. In GJA1 gene(exon 2) three novel mutations were detected: .400_402delAAG (in two families), с.461C>T (p.Thr154Ile) and с.94T>G (p.Phe32Val). In three sporadic cases de novo origin of mutations was proved by parents DNA testing; in family with affected mother and daughter mutation in the mother whose parents were unaffected also evidently occurred de novo .

глазо-зубо-пальцевой синдромген GJA1коннексин 43врожденные аномалии развитиясиндактилия III типаспастический парапарезлейкоэнцефалопатияoculodentodigital dysplasiagene GJA1connexin 43congenital anomaliessyndactyly type IIIspastic paraparesisleukoencephalopathyReferencesДжонс К. Наследственные синдромы по Дэвиду Смиту. Атлас-справочник. 6-е изд. Перевод с англ. М.: Практика, 2011. 318-321.Джонс К. Наследственные синдромы по Дэвиду Смиту. Атлас-справочник. 6-е изд. Перевод с англ. М.: Практика, 2011. 318-321.OMIM (On-line Mendelian Inheritance in Man) http://www.ncbi.nlm.nih.govOMIM (On-line Mendelian Inheritance in Man) http://www.ncbi.nlm.nih.govLoddenkemper T., Grote K., Evers S. et al. Neurological manifestations of the oculodentodigital dysplasia syndrome. J. Neurol. 2002; 49, 584-595.Loddenkemper T., Grote K., Evers S. et al. Neurological manifestations of the oculodentodigital dysplasia syndrome. J. Neurol. 2002; 49, 584-595.Richards S., Aziz N., Bale S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17: 405-424.Richards S., Aziz N., Bale S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17: 405-424.Willecke K., Jungbluth S., Dahl E. et al. Six genes of the human connexin gene family coding for gap junctional proteins are assigned to four different human chromosomes. Europ. J. Cell Biol. 1990; 53: 275-280.Willecke K., Jungbluth S., Dahl E. et al. Six genes of the human connexin gene family coding for gap junctional proteins are assigned to four different human chromosomes. Europ. J. Cell Biol. 1990; 53: 275-280.Corcos I., Meese E., Loch-Caruso R. Human connexin 43 gene locus, GJA1, sublocalized to band 6q21-q23.2. Cytogenet. Cell Genet. 1993; 64: 31-32.Corcos I., Meese E., Loch-Caruso R. Human connexin 43 gene locus, GJA1, sublocalized to band 6q21-q23.2. Cytogenet. Cell Genet. 1993; 64: 31-32.Gladwin A., Donnai D., Metcalfe K. et al. Localization of a gene for oculodentodigital syndrome to human chromosome 6q22-q24. Hum. Molec. Genet. 1997; 6: 123-127.Gladwin A., Donnai D., Metcalfe K. et al. Localization of a gene for oculodentodigital syndrome to human chromosome 6q22-q24. Hum. Molec. Genet. 1997; 6: 123-127.Boyadjiev S., Jabs E., LaBuda M. et al. Linkage analysis narrows the critical region for oculodentodigital dysplasia to chromosome 6q22-q23. Genomics. 1999; 58: 34-40Boyadjiev S., Jabs E., LaBuda M. et al. Linkage analysis narrows the critical region for oculodentodigital dysplasia to chromosome 6q22-q23. Genomics. 1999; 58: 34-40Paznekas W., Boyadjiev S., Shapiro R. et al. Connexin 43 (GJA1).mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. Am. J. Hum.Genet. 2003; 72, 408-418.Paznekas W., Boyadjiev S., Shapiro R. et al. Connexin 43 (GJA1).mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. Am. J. Hum.Genet. 2003; 72, 408-418.Gabriel L., Sachdeva R., Marcotty A. et al. Oculodentodigital dysplasia new ocular findings and a novel connexin 43 mutation. Arch. Ophthalmol. 2011; 129: 781-784.Gabriel L., Sachdeva R., Marcotty A. et al. Oculodentodigital dysplasia new ocular findings and a novel connexin 43 mutation. Arch. Ophthalmol. 2011; 129: 781-784.Vitiello C., D'Adamo P., Gentile F. et al. A novel GJA1 mutation causes oculodentodigital dysplasia without syndactyly. Am. J. Med Genet 2005; 133A: 58-60.Vitiello C., D'Adamo P., Gentile F. et al. A novel GJA1 mutation causes oculodentodigital dysplasia without syndactyly. Am. J. Med Genet 2005; 133A: 58-60.Van Norstrand D., Asimaki A., Rubinos C. et al. Connexin-43 mutation causes heterogeneous gap junction loss and sudden infant death. Circulation. 2012; 125, 474-481.Van Norstrand D., Asimaki A., Rubinos C. et al. Connexin-43 mutation causes heterogeneous gap junction loss and sudden infant death. Circulation. 2012; 125, 474-481.Laird D. Syndromic and non-syndromic disease-linked Cx43 mutations. FEBS Lett. 2014; 588: 1339-1348.Laird D. Syndromic and non-syndromic disease-linked Cx43 mutations. FEBS Lett. 2014; 588: 1339-1348.Paznekas W., Karczeski B., Vermeer S. et al. GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype. Hum.Mutat. 2009; 30, 724-733.Paznekas W., Karczeski B., Vermeer S. et al. GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype. Hum.Mutat. 2009; 30, 724-733.Avshalumova L., Fabrikant J., Koriakos A. Overview of skin diseases linked to connexin gene mutations. Int. J. Dermatol. 2014; 53: 192-205.Avshalumova L., Fabrikant J., Koriakos A. Overview of skin diseases linked to connexin gene mutations. Int. J. Dermatol. 2014; 53: 192-205.Opjordsmoen S., Nyberg-Hansen R. Hereditary spastic paraplegia with neurogenic bladder disturbances and syndactylia. Acta Neurol. Scand. 1980; 61: 35-41.Opjordsmoen S., Nyberg-Hansen R. Hereditary spastic paraplegia with neurogenic bladder disturbances and syndactylia. Acta Neurol. Scand. 1980; 61: 35-41.Colazza G., Di Gennaro G., Quarato P. et al. A case of a rare association of spastic paraplegia and type III syndactyly. Eur. J. Neurol. 2002; 9:105-107.Colazza G., Di Gennaro G., Quarato P. et al. A case of a rare association of spastic paraplegia and type III syndactyly. Eur. J. Neurol. 2002; 9:105-107.Gutmann D., Zackai E., McDonald-McGinn D. et al. Oculodentodigital dysplasia syndrome associated with abnormal cerebral white matter. Am. J. Med. Genet. 1991; 41:18-20.Gutmann D., Zackai E., McDonald-McGinn D. et al. Oculodentodigital dysplasia syndrome associated with abnormal cerebral white matter. Am. J. Med. Genet. 1991; 41:18-20.Amador C., Mathews A., Del Carmen Montoya M. et al. Expanding the neurologic phenotype of oculodentodigital dysplasia in a 4-generation Hispanic family. J. Child Neurol. 2008; 23, 901-905.Amador C., Mathews A., Del Carmen Montoya M. et al. Expanding the neurologic phenotype of oculodentodigital dysplasia in a 4-generation Hispanic family. J. Child Neurol. 2008; 23, 901-905.Barzegar M, Sayadnasiri M, Tabrizi A. Epilepsy as a rare neurologic manifestation of oculodentodigitalis dysplasia. Iran J. Child Neurol. 2012; 6: 39-43.Barzegar M, Sayadnasiri M, Tabrizi A. Epilepsy as a rare neurologic manifestation of oculodentodigitalis dysplasia. Iran J. Child Neurol. 2012; 6: 39-43.Furuta N., Ikeda M., Hirayanagi K. et al. A novel GJA1 mutation in oculodentodigita l dysplasia with progressive spastic paraplegia and sensory deficits. Intern. Med. 2012; 51, 93-98.Furuta N., Ikeda M., Hirayanagi K. et al. A novel GJA1 mutation in oculodentodigita l dysplasia with progressive spastic paraplegia and sensory deficits. Intern. Med. 2012; 51, 93-98.Jones C., Baldrighi C., Mills J. et al. Oculodentodigital dysplasia: ulnar-sided syndactyly and its associated disorders. J. Hand Surg. Am. 2011; 36: 1816-1821.Jones C., Baldrighi C., Mills J. et al. Oculodentodigital dysplasia: ulnar-sided syndactyly and its associated disorders. J. Hand Surg. Am. 2011; 36: 1816-1821.Shapiro R., Griffin J., Stine O. Evidence for genetic anticipation in the oculodentodigital syndrome. Am. J. Med. Genet. 1997; 71: 36-41.Shapiro R., Griffin J., Stine O. Evidence for genetic anticipation in the oculodentodigital syndrome. Am. J. Med. Genet. 1997; 71: 36-41.Ginsberg L., Jewett T., Grub R., McLean W. Oculodental digital dysplasia: neuroimaging in a kindred. Neuroradiology. 1996. 38: 84-86.Ginsberg L., Jewett T., Grub R., McLean W. Oculodental digital dysplasia: neuroimaging in a kindred. Neuroradiology. 1996. 38: 84-86.Ioan D., Dimitriu L., Belegeariu V., Fryns J. The oculo-dento-digital syndrome: male-to-male transmission and variable expression in a family. Genet. Couns. 1997; 8: 87-90.Ioan D., Dimitriu L., Belegeariu V., Fryns J. The oculo-dento-digital syndrome: male-to-male transmission and variable expression in a family. Genet. Couns. 1997; 8: 87-90.Himi M., Fujimaki T., Yokoyama T. et al. A case of oculodentodigital dysplasia syndrome with novel GJA1 gene mutation. Jpn. J. Ophthalmol. 2009; 53: 541-545.Himi M., Fujimaki T., Yokoyama T. et al. A case of oculodentodigital dysplasia syndrome with novel GJA1 gene mutation. Jpn. J. Ophthalmol. 2009; 53: 541-545.Huang X., Wang N., Xiao X., Li S., Zhang Q. A novel truncation mutation in GJA1 associated with open angle glaucoma and microcornea in a large Chinese family. Eye (Lond). 2015; 29: 972-977.Huang X., Wang N., Xiao X., Li S., Zhang Q. A novel truncation mutation in GJA1 associated with open angle glaucoma and microcornea in a large Chinese family. Eye (Lond). 2015; 29: 972-977.De la Parra D., Zenteno J. A new GJA1 (connexin 43) mutation causing oculodentodigital dysplasia associated to uncommon features. Ophthalmic Genet. 2007; 28: 198-202.De la Parra D., Zenteno J. A new GJA1 (connexin 43) mutation causing oculodentodigital dysplasia associated to uncommon features. Ophthalmic Genet. 2007; 28: 198-202.Doshi D., Limdi P., Parekh N., Gohil N. Oculodentodigital dysplasia. Indian J. Ophthalmol. 2016; 64: 227-230.Doshi D., Limdi P., Parekh N., Gohil N. Oculodentodigital dysplasia. Indian J. Ophthalmol. 2016; 64: 227-230.Amano K., Ishiguchi M., Aikawa T. et al. Cleft lip in oculodentodigital dysplasia suggests novel roles for connexin 43. J. Dent. Res. 2012; 91, 38S-44S.Amano K., Ishiguchi M., Aikawa T. et al. Cleft lip in oculodentodigital dysplasia suggests novel roles for connexin 43. J. Dent. Res. 2012; 91, 38S-44S.De Bock M., Kerrebrouck M., Wang N., Leybaert L. Neurological manifestations of oculodentodigital dysplasia: a Cx43 channelopathy of the central nervous system? Front. Pharmacol. 2013; 4: 120.De Bock M., Kerrebrouck M., Wang N., Leybaert L. Neurological manifestations of oculodentodigital dysplasia: a Cx43 channelopathy of the central nervous system? Front. Pharmacol. 2013; 4: 120.Feller L., Wood N., Sluiter M. et al. Report of a black South African child with oculodentodigital dysplasia and a novel GJA1 gene mutation. Am. J. Med. Genet. A. 2008; 146A: 1350-1353.Feller L., Wood N., Sluiter M. et al. Report of a black South African child with oculodentodigital dysplasia and a novel GJA1 gene mutation. Am. J. Med. Genet. A. 2008; 146A: 1350-1353.Porntaveetus T., Srichomthong C., Ohazama A., Suphapeetiporn K., Shotelersuk V. A novel GJA1 mutation in oculodentodigital dysplasia with extensive loss of enamel. Oral Dis. 2017 Mar 4. doi: 10.1111/odi.12663. [Epub ahead of print]Porntaveetus T., Srichomthong C., Ohazama A., Suphapeetiporn K., Shotelersuk V. A novel GJA1 mutation in oculodentodigital dysplasia with extensive loss of enamel. Oral Dis. 2017 Mar 4. doi: 10.1111/odi.12663. [Epub ahead of print]Brice G., Ostergaard P., Jeffery S. et al. A novel mutation in GJA1 causing oculodentodigital syndrome and primary lymphedema in a three generation family. Clin. Genet. 2013; 84, 378-381.Brice G., Ostergaard P., Jeffery S. et al. A novel mutation in GJA1 causing oculodentodigital syndrome and primary lymphedema in a three generation family. Clin. Genet. 2013; 84, 378-381.Wittlieb-Weber C., Haude K., Chin-To Fong, Vinocur J. A novel GJA1 mutation causing familial oculodentodigital dysplasia with dilated cardiomyopathy and arrhythmia. Heart Rhythm Case Reports. 2016; 2: 32-35.Wittlieb-Weber C., Haude K., Chin-To Fong, Vinocur J. A novel GJA1 mutation causing familial oculodentodigital dysplasia with dilated cardiomyopathy and arrhythmia. Heart Rhythm Case Reports. 2016; 2: 32-35.Izumi, K., Lippa A., Wilkens A. et al. Congenital heart defects in oculodentodigital dysplasia: report of two cases. Am. J. Med. Genet. A. 2013; 161: 3150-3154.Izumi, K., Lippa A., Wilkens A. et al. Congenital heart defects in oculodentodigital dysplasia: report of two cases. Am. J. Med. Genet. A. 2013; 161: 3150-3154.Kelly J., Esseltine J., Laird D. Specific functional pathologies of Cx43 mutations associated with oculodentodigital dysplasia 2016; 15: 2172-2185.Kelly J., Esseltine J., Laird D. Specific functional pathologies of Cx43 mutations associated with oculodentodigital dysplasia 2016; 15: 2172-2185.Gillespie F. A hereditary syndrome: «Dysplasia oculodentodigitalis». Arch. Ophthalmol. 1964; 71: 187-192.Gillespie F. A hereditary syndrome: «Dysplasia oculodentodigitalis». Arch. Ophthalmol. 1964; 71: 187-192.Beighton P, Hamersma H., Raad M. Oculodento-osseous dysplasia: heterogeneity or variable expression? Clin. Genet. 1979; 16: 169-177.Beighton P, Hamersma H., Raad M. Oculodento-osseous dysplasia: heterogeneity or variable expression? Clin. Genet. 1979; 16: 169-177.Traboulsi E., Faris B., Der Kalustian V. Persistent hyperplastic primary viteous and recessive oculodento-osseus dysplasia. Am. J. Med. Genet. 1986; 24: 95-10Traboulsi E., Faris B., Der Kalustian V. Persistent hyperplastic primary viteous and recessive oculodento-osseus dysplasia. Am. J. Med. Genet. 1986; 24: 95-10Frasson M., Calixto N., Cronemberger S. et al. Oculodentodigital dysplasia: study of ophthalmological and clinical manifestations in three boys with probably autosomal recessive inheritance. Ophthalmic Genet. 2004; 25: 227-236.Frasson M., Calixto N., Cronemberger S. et al. Oculodentodigital dysplasia: study of ophthalmological and clinical manifestations in three boys with probably autosomal recessive inheritance. Ophthalmic Genet. 2004; 25: 227-236.Richardson R., Joss S., Tomkin S. et al. A nonsense mutation in the first transmembrane domain of connexin 43 underlies autosomal recessive oculodentodigital syndrome. J. Med. Genet.Richardson R., Joss S., Tomkin S. et al. A nonsense mutation in the first transmembrane domain of connexin 43 underlies autosomal recessive oculodentodigital syndrome. J. Med. Genet.Joss S., Ghazawy S., Tomkins S. et al. Variable expression of neurological phenotype in autosomal recessive oculodentodigital dysplasia of two sibs and review of the literature. Eur. J. Pediatr. 2008; 167, 341-345.Joss S., Ghazawy S., Tomkins S. et al. Variable expression of neurological phenotype in autosomal recessive oculodentodigital dysplasia of two sibs and review of the literature. Eur. J. Pediatr. 2008; 167, 341-345.Pizzuti A., Flex E., Mingarelli R., Salpietro C., Zelante L., Dallapiccola B. A homozygous GJA1 gene mutation causes a Hallermann-Streiff/ODDD spectrum phenotype. Hum Mutat 2004; 23: 286.Pizzuti A., Flex E., Mingarelli R., Salpietro C., Zelante L., Dallapiccola B. A homozygous GJA1 gene mutation causes a Hallermann-Streiff/ODDD spectrum phenotype. Hum Mutat 2004; 23: 286.Huang T., Shao Q.,Macdonald A. et al. Autosomal recessive GJA1 (Cx43) gene mutations cause oculodentodigital dysplasia by distinct mechanisms. J. Cell Sci. 2013; 126, 2857-2866.Huang T., Shao Q.,Macdonald A. et al. Autosomal recessive GJA1 (Cx43) gene mutations cause oculodentodigital dysplasia by distinct mechanisms. J. Cell Sci. 2013; 126, 2857-2866.Kelly J., Simek J., Laird D. Mechanisms linking connexin mutations to human diseases. Cell Tissue Res. 2015; 360: 701-721.Kelly J., Simek J., Laird D. Mechanisms linking connexin mutations to human diseases. Cell Tissue Res. 2015; 360: 701-721.Alao M., Bonneau D., Holder- Espinasse M. et al. Oculo-dento-digital dysplasia: lack of genotype- phenotype correlation for GJA1 mutations and usefulness of neuroimaging. Eur.J.Med.Genet. 2010; 53, 19-22.Alao M., Bonneau D., Holder- Espinasse M. et al. Oculo-dento-digital dysplasia: lack of genotype- phenotype correlation for GJA1 mutations and usefulness of neuroimaging. Eur.J.Med.Genet. 2010; 53, 19-22.Wang N., DeVuyst E., Ponsaerts R. et al. Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia/reperfusion injury. Basic Res. Cardiol. 2013; 108, 309.Wang N., DeVuyst E., Ponsaerts R. et al. Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia/reperfusion injury. Basic Res. Cardiol. 2013; 108, 309.Wiencken-Barger A., Djukic B., Casper K. et al. A role for Connexin43 during neurodevelopment. Glia. 2007; 55, 675-686.Wiencken-Barger A., Djukic B., Casper K. et al. A role for Connexin43 during neurodevelopment. Glia. 2007; 55, 675-686.Kalcheva N., Qu J., Sandeep N. et al. Gap junction remodeling and cardiac arrhythmogenesis in a murine model of oculodentodigital dysplasia. Proc. Nat. Acad. Sci. USA. 2007; 104: 20512-20516.Kalcheva N., Qu J., Sandeep N. et al. Gap junction remodeling and cardiac arrhythmogenesis in a murine model of oculodentodigital dysplasia. Proc. Nat. Acad. Sci. USA. 2007; 104: 20512-20516.Dobrowolski R., Sommershof A., Willecke K. Some oculodentodigital dysplasia-associated Cx43 mutations cause increased hemichannel activity in addition to deficient gap junction channels. J. Membr.Biol. 2007; 219: 9-17.Dobrowolski R., Sommershof A., Willecke K. Some oculodentodigital dysplasia-associated Cx43 mutations cause increased hemichannel activity in addition to deficient gap junction channels. J. Membr.Biol. 2007; 219: 9-17.Dobrowolski R., Sasse P., Schrickel J. et al. The conditional connexin 43 G138R mouse mutant represents a new model of hereditary oculodentodigital dysplasia in humans. Hum.Mol.Genet. 2008; 17: 539-554.Dobrowolski R., Sasse P., Schrickel J. et al. The conditional connexin 43 G138R mouse mutant represents a new model of hereditary oculodentodigital dysplasia in humans. Hum.Mol.Genet. 2008; 17: 539-554.Fenwick A., Richardson R., Butterworth J. et al. Novel mutations in GJA1 cause oculodentodigital syndrome. J. Dent. Res. 2008; 87, 1021-1026.Fenwick A., Richardson R., Butterworth J. et al. Novel mutations in GJA1 cause oculodentodigital syndrome. J. Dent. Res. 2008; 87, 1021-1026.Churko J., Chan J., Shao Q., Laird D. The G60S connexin43 mutant regulates hair growth and hair fiber morphology in a mouse model of human oculodentodigital dysplasia. J. Invest. Dermatol. 2011; 131: 2197-2204.Churko J., Chan J., Shao Q., Laird D. The G60S connexin43 mutant regulates hair growth and hair fiber morphology in a mouse model of human oculodentodigital dysplasia. J. Invest. Dermatol. 2011; 131: 2197-2204.Stewart M., Gong, X., Barr K. et al. The severity of mammary gland developmental defects is linked to the overall functional status of Cx43 as revealed by genetically modified mice. Biochem. J. 2013; 449: 401-413.Stewart M., Gong, X., Barr K. et al. The severity of mammary gland developmental defects is linked to the overall functional status of Cx43 as revealed by genetically modified mice. Biochem. J. 2013; 449: 401-413.Huang T., Shao Q., Barr K. et al. Myogenic bladder defects in mouse models of human oculodentodigital dysplasia. Biochem J. 2014; 457:441-449.Huang T., Shao Q., Barr K. et al. Myogenic bladder defects in mouse models of human oculodentodigital dysplasia. Biochem J. 2014; 457:441-449.Shuja Z., Li L., Gupta S. et al. Connexin26 mutations causing palmoplantar keratoderma and deafness interact with connexin43, modifying gap junction and hemichannel properties. J Invest. Dermatol. 2016; 136: 225-235.Shuja Z., Li L., Gupta S. et al. Connexin26 mutations causing palmoplantar keratoderma and deafness interact with connexin43, modifying gap junction and hemichannel properties. J Invest. Dermatol. 2016; 136: 225-235.

The authors declare that there are no conflicts of interest present.