Author/Editor		Writzl, Karin
Title		Delecija v genu NEMO pri bolnikih z inkontinenco pigmenta
Type		monografija
Place		Ljubljana
Publisher		Medicinska fakulteta
Publication year		2002
Volume		str. 38
Language		slo
Abstract		Incontinentia pigmenti (IP) is a genodermatosis that segregates as an X-linked dominant disorder and is in males usually lethal prenatally. This disorder demonstrates an almost complete penetrance, but its phenotypic expression is highly variable, even among related patients with the same mutation. In affected females it causes variable abnormalities of the skin, hair, nails, teeth, eyes and central nervous system The IP locus has been mapped to Xq28, and recently, after more than a decade of genetic linkage analysis, an international consortium of laboratories has managed to identify the gene that is mutated in individuals with IP as the NEMO gene (NF-kappaB Essential Modulator), which encodes NEMO protein. The NEMO protein is the regulatory component of IkappaB kinase, and is essential to activation of the NF-kappaB transcription factor, which participates in many immune and inflammatory pathways and prevents apoptosis in response to TNF-alpha. Approximately 80 % of patients were shown to carry a common deletion mutation that removes exons 4 through 10 of the NEMO gene (NEMOdelta4-70), leading to the generation of aberrant NEMO message. The aim of this study was to assess how this mutation is spread among our population of patients with IP, and to examine the extent of clinical heterogeneity of these patients and its relation to the presence or absence of NEMOdelta4-70. Ten Slovene families (of the 14 female patients there were 10 probands) were included in this study. Polymerase chain reaction (PCR) analysis was used for the detection of the NEMO gene deletion. Fourprobands showed a delefion of the NEMO gene. The phenotypic expression was highly variable, even among related patients with-a NEMO deletion.
Summary		Inkontinenca pigments (IP) je na kromosom X vezano dominantno obolenje, ki prizadene ektodermalna tkiva in je pri moških v večni primerov že prenatalno smrtna. Penetranca IP je popolna, stopnja ekspresije pa je izredno raznolika celo znotraj iste družine. Bolezen se v večini primerov kaže s prizadetostjo kože, las, zob in nohtov, pri najhujši obliki pa z duševno manjrazvitostjo in slepoto, ki je posledica odstopa mrežnice. Do nedavnega je bila diagnoza mogoča samo glade na klinične znake, z razvojem molekularne genetike pa so v obsežni raziskavi vezavne analize lokalizirali tarčno območje Xq28, na katerem so lets 2000 našli tudi gen NEMO (angl.; NF-kapaB essential modulator), katerega mutacija vodi v nastanek inkontinence pigments. Gen NEMO nosi zapis za gama podenoto večproteinskega kinaznega kompleksa, ki ima glavno vlogo pri regulacijski poti jedrnega faktorja kapaB, ki je vključen v imunski in vnetni odgovor tar v regulacijo apoptoze. Najpogostejša mutacija gena NEMO je delecija 4. do 10. eksona (NEMOdelta4-10). Namen raziskave je bila določitev pogostosti delecije NEMOdelta4-10 pri slovenskih bolnikih z inkontinenco pigmenta. Želeli smo tudi primerjati fenotipske razfičnosti med bolniki z delecijo NEMOdelta4-10 in bolniki brez delecije NEMOdelta4-10. V raziskavo smo vključili 14 bolnic, pri katerih je bila klinično postavljena diagnoza IP in z metodo verižne polimerazne reakcije (PCR) preverili prisotnost delecije NEMOdelta4-10. Delecijo NEMOdelta4-10 smo dokazali pri štirih od desetih slovenskih bolnic z IP, ki niso bile v sorodu. Potrdili smo, da so bolniki z IP fenotipsko zelo različni. Tudi pri genetsko homogeni skupini z delecijo NEMOdelta4-10 so bile razlike v prizadetosti precejšnje, celo pri bolnikih iz iste družine.
Descriptors		INCONTINENTIA PIGMENTI GENE DELETION PHENOTYPE POLYMERASE CHAIN REACTION GENOTYPE