RESUMEN
Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.
Asunto(s)
Cerebelo/anomalías , Endorribonucleasas/genética , Mutación , Puente/anomalías , Encéfalo/metabolismo , Mapeo Cromosómico , Cromosomas Humanos Par 17 , Humanos , Modelos Moleculares , Polimorfismo de Nucleótido Simple , SíndromeRESUMEN
Cleidocranial Dysplasia (CCD) is an autosomal dominant skeletal disorder characterized by hypoplastic or absent clavicles, increased head circumference, large fontanels, dental anomalies, and short stature. Hand malformations are also common. Mutations in RUNX2 cause CCD, but are not identified in all CCD patients. In this study we screened 135 unrelated patients with the clinical diagnosis of CCD for RUNX2 mutations by sequencing analysis and demonstrated 82 mutations 48 of which were novel. By quantitative PCR we screened the remaining 53 unrelated patients for copy number variations in the RUNX2 gene. Heterozygous deletions of different size were identified in 13 patients, and a duplication of the exons 1 to 4 of the RUNX2 gene in one patient. Thus, heterozygous deletions or duplications affecting the RUNX2 gene may be present in about 10% of all patients with a clinical diagnosis of CCD which corresponds to 26% of individuals with normal results on sequencing analysis. We therefore suggest that screening for intragenic deletions and duplications by qPCR or MLPA should be considered for patients with CCD phenotype in whom DNA sequencing does not reveal a causative RUNX2 mutation.
Asunto(s)
Displasia Cleidocraneal/genética , Eliminación de Gen , Análisis Mutacional de ADN , Heterocigoto , Humanos , Reacción en Cadena de la PolimerasaRESUMEN
In patients with guanidinoacetate methyltransferase (GAMT) deficiency several parameters may point towards the diagnosis of GAMT deficiency. These include the low levels of creatine and creatinine in urine, the high concentration of guanidinoacetic acid (GAA) in urine and the low levels of creatine and creatinine in the cerebrospinal fluid (CSF). In this study, body fluids from 10 GAMT deficient patients were analysed using (1)H NMR spectroscopy. The urine 1D (1)H NMR spectra of all the patients showed a doublet resonance at 3.98 ppm (pH 2.50) derived from GAA present in high concentration. For this compound, a good recovery and good correlation was found between an LC-MS/MS method and (1)H NMR spectroscopy. In CSF NMR spectra of these patients, the singlet resonances of creatine and creatinine (3.05 and 3.13 ppm, respectively) were absent (normally always present in (1)H NMR spectra of CSF). Due to overlap by other resonances, the doublet of GAA could not be observed. Our data demonstrate that (1)H NMR spectroscopy of urine and CSF can be used to diagnose patients with GAMT deficiency.
Asunto(s)
Líquidos Corporales/enzimología , Guanidinoacetato N-Metiltransferasa/deficiencia , Espectroscopía de Resonancia Magnética/métodos , Protones , Adulto , Niño , Preescolar , Creatina/biosíntesis , Femenino , Glicina/análogos & derivados , Glicina/sangre , Glicina/líquido cefalorraquídeo , Glicina/química , Glicina/orina , Humanos , Concentración de Iones de Hidrógeno , Lactante , Masculino , Valores de ReferenciaRESUMEN
Fibroblast growth factor 23 (FGF-23) is a recently identified hormone that is of prime importance for phosphate homeostasis in humans. FGF-23 is secreted by osteocytes in response to phosphate-loading. It stimulates renal phosphate excretion and suppresses the formation of 1.25-dihydroxy-vitamin D by inhibiting renal 1α-hydroxylase activity. Knowledge about FGF-23 in early infancy is limited. We report here the case of a newborn with transient secondary hypoparathyroidism caused by maternal primary hyperparathyroidism during pregnancy. FGF-23 levels at birth were extremely high in the child (15.850 kilo-Relative Units per liter, kRU/L) (ie, â¼45 times higher than in the mother) and â¼7 times higher than in healthy newborns. The child's FGF-23 levels declined gradually and reached the normal adult range after â¼7 months. We discuss the potential physiologic significance of FGF-23 in newborns.
Asunto(s)
Factores de Crecimiento de Fibroblastos/sangre , Hiperparatiroidismo Secundario/etiología , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Hiperparatiroidismo Secundario/sangre , Hipertensión/sangre , Hipertensión/complicaciones , Recién Nacido , Masculino , Embarazo , Complicaciones Cardiovasculares del Embarazo/sangreRESUMEN
Since vacuum-related neonatal morbidity has been described in many studies clinical observation of neonates is common practice after vacuum-assisted vaginal delivery. However, no guidelines are available regarding the required length of hospital stay of these infants, because little is known about the first onset of complaints due to vacuum extraction-related morbidity. In a prospective observational cohort study we found that vacuum extraction-related complaints occurred in term neonates within 10 h following birth. Mild to moderate morbidity was frequently seen, whereas severe morbidity was infrequently seen. Previous artificial delivery, Apgar score lower than 7 at 1 min, and birth weight >4.0 kg were risk factors for morbidity after vacuum extraction. We suggest that it is justified to discharge neonates at least 10 h after vacuum delivery when no vacuum extraction-related complaints have occurred.
Asunto(s)
Extracción Obstétrica por Aspiración/efectos adversos , Puntaje de Apgar , Peso al Nacer , Femenino , Humanos , Recién Nacido , Análisis Multivariante , Embarazo , Resultado del Embarazo , Estudios Prospectivos , Factores de Riesgo , Extracción Obstétrica por Aspiración/estadística & datos numéricosRESUMEN
OBJECTIVE: To investigate myo-inositol, glucose and zinc status in mothers and their infants on cleft lip with or without cleft palate risk (CLP). DESIGN: Case-control study. SETTING: University Medical Centre Nijmegen, the Netherlands. POPULATION: Eighty-four mothers and their CLP child and 102 mothers and their healthy child. METHODS: Venous blood samples were obtained to determine serum myo-inositol and glucose and red blood cell zinc concentrations in mothers and children. Geometric means were calculated and compared between the groups. The blood parameters were dichotomised with cutoff points based on control values,