RESUMEN
De novo variants in QRICH1 (Glutamine-rich protein 1) has recently been reported in 11 individuals with intellectual disability (ID). The function of QRICH1 is largely unknown but it is likely to play a key role in the unfolded response of endoplasmic reticulum stress through transcriptional control of proteostasis. In this study, we present 27 additional individuals and delineate the clinical and molecular spectrum of the individuals (n = 38) with QRICH1 variants. The main clinical features were mild to moderate developmental delay/ID (71%), nonspecific facial dysmorphism (92%) and hypotonia (39%). Additional findings included poor weight gain (29%), short stature (29%), autism spectrum disorder (29%), seizures (24%) and scoliosis (18%). Minor structural brain abnormalities were reported in 52% of the individuals with brain imaging. Truncating or splice variants were found in 28 individuals and 10 had missense variants. Four variants were inherited from mildly affected parents. This study confirms that heterozygous QRICH1 variants cause a neurodevelopmental disorder including short stature and expands the phenotypic spectrum to include poor weight gain, scoliosis, hypotonia, minor structural brain anomalies, and seizures. Inherited variants from mildly affected parents are reported for the first time, suggesting variable expressivity.
Asunto(s)
Trastorno del Espectro Autista , Enanismo , Discapacidad Intelectual , Trastornos del Neurodesarrollo , Escoliosis , Trastorno del Espectro Autista/genética , Humanos , Discapacidad Intelectual/genética , Hipotonía Muscular , Trastornos del Neurodesarrollo/genética , Convulsiones , Aumento de PesoRESUMEN
Submicroscopic terminal 6q deletions are rare. We report on two familial submicroscopic terminal 6q deletions ascertained because of prenatally detected isolated ventriculomegaly and further delineate the variable prenatal and postnatal phenotype. We review published cases of <5 Mb terminal 6q deletions.
Asunto(s)
Hidrocefalia/genética , Anomalías Múltiples/genética , Adulto , Deleción Cromosómica , Cromosomas Humanos Par 6/fisiología , Femenino , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/diagnóstico por imagen , Lactante , Recién Nacido , Cariotipificación , Masculino , Fenotipo , Embarazo , UltrasonografíaRESUMEN
Distal interstitial deletions of chromosome 14 involving the 14q24-q23.2 region are rare, and only been reported so far in 20 patients. Ten of these patients were analyzed both clinically and genetically. Here we present a de novo interstitial deletion of chromosome 14q24.3-q32.2 in a male patient with developmental delay, language impairment, plagiocephaly, BPES features (blepharophimosis, ptosis, epicanthus), and congenital heart defect. The deletion breakpoints were fine mapped using fluorescence in situ hybridization (FISH) and the size of the deletion is estimated to be approximately 23 Mb. Based on genotype-phenotype comparisons of the 10 previously published patients and the present case, we suggest that the shortest regions for deletion overlap may include candidate genes for speech impairment, mental retardation, and hypotonia.
Asunto(s)
Anomalías Múltiples/genética , Discapacidades del Desarrollo/genética , Cardiopatías Congénitas/genética , Fenotipo , Plagiocefalia/genética , Anomalías Múltiples/patología , Deleción Cromosómica , Cromosomas Humanos Par 14/genética , Discapacidades del Desarrollo/patología , Cardiopatías Congénitas/patología , Humanos , Hibridación Fluorescente in Situ , Masculino , Plagiocefalia/patologíaRESUMEN
We describe a case of fatal pneumonia in a previously healthy 14-year-old boy. The patient was severely affected at the time of admission with high fever, tachypnea, tachycardia and peripheral cyanosis. The condition worsened despite treatment with antibiotics as well as respiratory and pressure support. Acidosis and critical leucopenia supervened and the patient died just short of 24 hours after admission. Subsequent bacterial cultivation showed Panton-Valentine Leucocidin-producing Staphylococcus aureus.
