Клинико-молекулярно-генетические характеристики глазо-зубо-пальцевого синдрома

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 .

глазо-зубо-пальцевой синдром, ген GJA1, коннексин 43, врожденные аномалии развития, синдактилия III типа, спастический парапарез, лейкоэнцефалопатия, oculodentodigital dysplasia, gene GJA1, connexin 43, congenital anomalies, syndactyly type III, spastic paraparesis, leukoencephalopathy

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