CONTEXT: Collagens are the most abundant proteins in the human body. In a growth plate, collagen types II, IX, X, and XI are present. Defects in collagen genes cause heterogeneous syndromic disorders frequently associated with short stature. Less is known about oligosymptomatic collagenopathies. OBJECTIVE: This work aims to evaluate the frequency of collagenopathies in familial short stature (FSS) children and to describe their phenotype, including growth hormone (GH) treatment response. METHODS: Eighty-seven FSS children (pretreatment height ≤ -2 SD both in the patient and his or her shorter parent) treated with GH were included in the study. Next-generation sequencing was performed to search for variants in the COL2A1, COL9A1, COL9A2, COL9A3, COL10A1, COL11A1, and COL11A2 genes. The results were evaluated using American College of Medical Genetics and Genomics guidelines. The GH treatment response of affected children was retrospectively evaluated. RESULTS: A likely pathogenic variant in the collagen gene was found in 10 of 87 (11.5%) children. Detailed examination described mild asymmetry with shorter limbs and mild bone dysplasia signs in 2 of 10 and 4 of 10 affected children, respectively. Their growth velocity improved from a median of 5.3 cm/year to 8.7 cm/year after 1 year of treatment. Their height improved from a median of -3.1 SD to -2.6 SD and to -2.2 SD after 1 and 3 years of therapy, respectively. The final height reached by 4 of 10 children differed by -0.67 to +1.0 SD and -0.45 to +0.5 SD compared to their pretreatment height and their affected untreated parent's height, respectively. CONCLUSION: Oligosymptomatic collagenopathies are a frequent cause of FSS. The short-term response to GH treatment is promising.

• Klíčová slova
• collagenopathies, familial short stature, growth hormone treatment, growth plate, next-generation sequencing,
• MeSH
• databáze faktografické MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• genetické asociační studie MeSH
• kolagen typ XI genetika   MeSH
• kolagen nedostatek   genetika   MeSH
• lidé MeSH
• lidský růstový hormon nedostatek   terapeutické užití   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• poruchy růstu * farmakoterapie   epidemiologie   genetika   patologie   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• růstová ploténka růst a vývoj   metabolismus   patologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• COL11A1 protein, human MeSH Prohlížeč
• COL11A2 protein, human MeSH Prohlížeč
• kolagen typ XI MeSH
• kolagen MeSH
• lidský růstový hormon MeSH

This study aimed to define the differences in growth characteristics in the three most frequent causes of growth retardation - growth hormone deficiency, hypothyreosis and constitutional delay of growth and development - in order to provide diagnostic means for distinguishing these disorders. The study included 166 children with growth disorders aged 4-18 years. The height for age, the bone age using the TW3 method, the predicted height as the target height and the current prediction using the TW3 method were studied. For bone age, the radius, ulna and short bones compartment (RUS) and carpal bones (CARP) were evaluated separately and the difference in their delay in relation to chronological age (ΔBA_RUS_CARP) was determined. The relationship of the studied variables with sex and the underlying diagnosis was tested and the relationship of hypothyreosis and growth data was estimated. The model was tested on the growth data of 104 randomly selected patients with a growth disorder. The largest significant distinction was demonstrated by the difference ΔBA_RUS_CARP in hypothyreosis. The created linear regression model was highly statistically significant (χ2 = 19.4, p < 0.0001) and showed high selectivity (0.609, 95% CI 0.409; 0.808) as well as high specificity (0.864, 95% CI 0.781; 0.946). The clinical validity of the model demonstrated a 61% predictive value for the detection and an 81% successful specification of hypothyreosis. The study demonstrated the possibility of distinguishing suspected hypothyreosis from other causes of growth retardation based on differences in severity of the ossification delay in skeletal compartments of the hand.

• Klíčová slova
• Bone age, Constitutional delay of growth and development, Diagnostic model, Growth hormone deficiency, Short stature,
• MeSH
• biologické modely MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• hypotyreóza diagnóza   patologie   MeSH
• kosti zápěstní patologie   MeSH
• lidé MeSH
• lidský růstový hormon nedostatek   MeSH
• lineární modely MeSH
• mladiství MeSH
• poruchy růstu diagnóza   patologie   MeSH
• předškolní dítě MeSH
• radius patologie   MeSH
• tělesná výška MeSH
• ulna patologie   MeSH
• určení kostního věku MeSH
• vývoj kostí MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lidský růstový hormon MeSH

BACKGROUND: Terminal Xp deletion leads to SHOX haploinsufficiency, and when it exceeds Xp22.33 it causes a variant of Turner syndrome (TS) in which gonadal function is preserved and short stature constitutes the major clinical feature. CASE REPORT: We present a family with vertical transmission of TS that affected six women in four sequential generations. The karyotype was defined as a combination of terminal Xp deletion and terminal Xq duplication: 46,X,rec(X)inv(p21.1q27.3). All affected women had short stature, but had developed spontaneous puberty and normal fertility. Generation IV exclusively received recombinant human growth hormone (rhGH). We investigated the effect of rhGH treatment on skeletal growth and body proportion via the comparison of auxological data from an untreated 39.7-year-old mother to her 14.8-year-old rhGH-treated daughter. The adult height of the daughter was substantially better than that of the mother [160.3 cm (-0.8 SDS) and 150.0 cm (-2.7 SDS), respectively]; however, the disproportion progressed following rhGH treatment and ultimately led to a worse trunk-to-extremities ratio compared with the mother (4.8 and 3.7 SDS, respectively). CONCLUSION: This rare family confirms the vertical transmission of TS spanning multiple generations. The combination of endogenous estrogen production and exogenous rhGH administration in women with SHOX haploinsufficiency may worsen their body disproportion.

• MeSH
• dítě MeSH
• dospělí MeSH
• estrogeny aplikace a dávkování   MeSH
• homeodoménové proteiny genetika   MeSH
• lidé MeSH
• lidský růstový hormon aplikace a dávkování   MeSH
• mladiství MeSH
• poruchy růstu * farmakoterapie   genetika   patologie   MeSH
• protein SHOX MeSH
• růstový hormon aplikace a dávkování   MeSH
• Turnerův syndrom * farmakoterapie   genetika   patologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• estrogeny MeSH
• homeodoménové proteiny MeSH
• lidský růstový hormon MeSH
• protein SHOX MeSH
• růstový hormon MeSH
• SHOX protein, human MeSH Prohlížeč

The genetic cause of GAPO syndrome, a condition characterized by growth retardation, alopecia, pseudoanodontia, and progressive visual impairment, has not previously been identified. We studied four ethnically unrelated affected individuals and identified homozygous nonsense mutations (c.262C>T [p.Arg88*] and c.505C>T [p.Arg169*]) or splicing mutations (c.1435-12A>G [p.Gly479Phefs*119]) in ANTXR1, which encodes anthrax toxin receptor 1. The nonsense mutations predictably trigger nonsense-mediated mRNA decay, resulting in the loss of ANTXR1. The transcript with the splicing mutation theoretically encodes a truncated ANTXR1 containing a neopeptide composed of 118 unique amino acids in its C terminus. GAPO syndrome's major phenotypic features, which include dental abnormalities and the accumulation of extracellular matrix, recapitulate those found in Antxr1-mutant mice and point toward an underlying defect in extracellular-matrix regulation. Thus, we propose that mutations affecting ANTXR1 function are responsible for this disease's characteristic generalized defect in extracellular-matrix homeostasis.

• MeSH
• alopecie genetika   patologie   MeSH
• alternativní sestřih genetika   MeSH
• anodoncie genetika   patologie   MeSH
• dědičné atrofie optického nervu genetika   patologie   MeSH
• DNA primery genetika   MeSH
• extracelulární matrix genetika   metabolismus   MeSH
• fibroblasty MeSH
• fluorescenční protilátková technika MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci genetika   MeSH
• homeostáza genetika   MeSH
• lidé MeSH
• lidské chromozomy, pár 2 genetika   MeSH
• mikrofilamentové proteiny MeSH
• místa sestřihu RNA genetika   MeSH
• molekulární sekvence - údaje MeSH
• nádorové proteiny genetika   MeSH
• nesmyslný kodon genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• poruchy růstu genetika   patologie   MeSH
• receptory buněčného povrchu genetika   MeSH
• rodokmen MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• ANTXR1 protein, human MeSH Prohlížeč
• DNA primery MeSH
• mikrofilamentové proteiny MeSH
• místa sestřihu RNA MeSH
• nádorové proteiny MeSH
• nesmyslný kodon MeSH
• receptory buněčného povrchu MeSH

Ossification in 4-week-old nu/nu and nu/+ BALB/c and BFU mice was studied by X-ray analysis and by measurement of the thickness of the proximal tibial growth cartilage using CUE 4 Olympus computer image analysis. Not only altered architecture but also a significantly thinner proximal tibial growth plate was observed in athymic nu/nu as opposed to nu/+ and BFU mice. On the other hand, no significant differences were found between nu/+ and BFU littermates. Higher X-ray density of tail vertebrae was observed in nu/+ and BFU than in nu/nu mice. This comparison between athymic nu/nu and hairless euthymic BFU mice indicates that altered postnatal ossification in nude mice is not caused by hairlessness, but is due to other (immunological or endocrinological) differences.

• MeSH
• heterozygot MeSH
• kostní denzita MeSH
• myši bezsrsté růst a vývoj   MeSH
• myši inbrední BALB C MeSH
• myši nahé růst a vývoj   MeSH
• myši MeSH
• ocas diagnostické zobrazování   MeSH
• osteogeneze * MeSH
• počítačové zpracování obrazu * MeSH
• poruchy růstu diagnostické zobrazování   genetika   patologie   MeSH
• rentgendiagnostika MeSH
• růstová ploténka ultrastruktura   MeSH
• tibie ultrastruktura   MeSH
• vývoj kostí * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH