A SHOX géndeletio előfordulása idiopáthiás alacsonynövésben. Multicentrikus tanulmány | The prevalence of SHOX gene deletion in children with idiopathic short stature.A multicentric study
2017
Absztrakt: Bevezetes: A SHOX gen izolalt
haploinsufficientiaja az alacsonynovest okozo monogenes elvaltozasok
leggyakoribb oka. A gen heterozigota elterese az idiopathias alacsonynovessel
(ISS) diagnosztizalt betegek 2–15%-aban, Leri–Weill-dyschondrosteosis szindroma
(LWS) 50–90%-aban, valamint a Turner-szindromaban szenvedők csaknem 100%-aban
igazolhato. Celkitűzes: A SHOX gen
haploinsufficientiaja gyakorisaganak meghatarozasa ISS-sel es LWS-sel
diagnosztizalt, valamint Turner-fenotipusu, de normalis karyotypussal rendelkező
betegek (TF) koreben, valamint beazonositani a SHOX
genelteresre jellemző dysmorphias jeleket. Modszer: Osszesen
144 betegben kerult sor a SHOX gen
haploinsufficientia-vizsgalatara multiplex ligatios proba Amplifikacio (MLPA)
modszerrel. A betegek klinikai adatai (auxologiai parameterek, csontrendszeri
rendellenessegek, dysmorphias tunetek) es a pozitiv genotipus kozotti
osszefuggeseket statisztikai modszerekkel elemeztek.
Eredmenyek: A vizsgalt 144 betegből 11 (7,6%) eseteben
igazolodott SHOX genelteres, női dominanciaval (8/11, 81%). A
SHOX-pozitiv betegeknek szignifikansan magasabb volt a
testtomegindexe (BMI) (5/11-ből vs. 20/133-bol mutatott emelkedett erteket,
p<0,02), es gyakoribbak voltak a dysmorphias tunetek (9/11 vs. 62/133, p =
0,02). A felső vegtagokon megjelenő Madelung-deformitas
SHOX-pozitiv betegek kozott szinten szignifikansan gyakrabban
fordult elő (4/11, 36% vs. 14/133, 10%, p = 0,0066), mint a
SHOX-negativakban, de a vizsgalatkori eletkor, az
alacsonynoves merteke, valamint az auxologiai meresek alapjan szamolt
testaranyok nem mutattak statisztikailag kimutathato kulonbseget a ket csoport
kozott. Kovetkeztetesek: A SHOX gen
haploinsufficientiajanak előfordulasi gyakorisaga a vizsgalt betegpopulacionkban
megegyezik az irodalmi adatokkal. SHOX-pozitiv esetekben, az
idiopathias alacsonynoves mellett, a dysmorphias elvaltozasok pozitiv prediktiv
ertekkel birnak a SHOX genelvaltozasok fennallasara. Ugyanakkor
a dysmorphias jegyet nem mutato, de genetikailag pozitiv eset arra utal, hogy a
SHOX gen vizsgalata indokolt dysmorphias tunetet nem mutato
idiopathias alacsonynoves eseten is. Orv Hetil. 2017; 158(34): 1351–1356.
| Abstract: Introduction: The isolated haploinsufficiency of the
SHOX gene is one of the most common cause of short stature
determined by monogenic mutations. The heterozygous deviation of the gene can be
detected in 2–15% of patients with idiopathic short stature (ISS), in 50–90% of
patients with Leri-Weill dyschondrosteosis syndrome (LWS), and in almost 100% of
patients with Turner syndrome. Aim: The aim of our study was to
evaluate the frequency of SHOX gene haploinsufficiency in
children with ISS, LWS and in patients having Turner syndrome phenotype (TF),
but normal karyotype, and to identify the dysmorphic signs characteristic for
SHOX gene deficiency. Method: A total of
144 patients were included in the study. Multiplex Ligation-dependent Probe
Amplification (MLPA) method was used to identify the SHOX gene
haploinsufficiency. The relationships between clinical data (axiological
parameters, skeletal disorders, dysmorphic signs) and genotype were analyzed by
statistical methods. Results: 11 (7.6%) of the 144 patients
showed SHOX gene deficiency with female dominance (8/11, 81%
female). The SHOX positive patients had a significantly higher
BMI (in 5/11 vs. 20/133 cases, p<0.02) and presented more frequent dysmorphic
signs (9/11vs 62/133, p = 0.02). Madelung deformity of the upper limbs was also
significantly more frequent among the SHOX positive patients
(4/11, i.e. 36%, vs. 14/133, i.e. 10%, p = 0.0066). There were no statistically
significant differences between the mean age, mean height and auxological
measurements (sitting height/height, arm span/height) between the two groups of
patients. Conclusions: The occurrence of SHOX
gene haploinsufficiency observed in our population corresponds to the literature
data. In SHOX positive patients, in addition to short stature,
the dysmorphic signs have a positive predictive value for SHOX
gene alterations. However, the SHOX deletion detected in a
patient with idiopathic short stature without dysmorphic signs suggest that
SHOX deletion analysis can be recommended in patients with
ISS. Orv Hetil. 2017; 158(34): 1351–1356.
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