ABSTRACT
Schinzel-Giedion syndrome (SGS) is a severe multisystem disorder characterized by distinctive facial features, profound intellectual disability, refractory epilepsy, cortical visual impairment, hearing loss, and various congenital anomalies. SGS is attributed to gain-of-function (GoF) variants in the SETBP1 gene, with reported variants causing canonical SGS located within a 12 bp hotspot region encoding SETBP1 residues aa868-871 (degron). Here, we describe a case of typical SGS caused by a novel heterozygous missense variant, D874V, adjacent to the degron. The female patient was diagnosed in the neonatal period and presented with characteristic facial phenotype (midface retraction, prominent forehead, and low-set ears), bilateral symmetrical talipes equinovarus, overlapping toes, and severe bilateral hydronephrosis accompanied by congenital heart disease, consistent with canonical SGS. This is the first report of a typical SGS caused by a, SETBP1 non-degron missense variant. This case expands the genetic spectrum of SGS and provides new insights into genotype-phenotype correlations.
Subject(s)
Abnormalities, Multiple , Carrier Proteins , Hand Deformities, Congenital , Mutation, Missense , Nails, Malformed , Humans , Female , Abnormalities, Multiple/genetics , Carrier Proteins/genetics , Infant, Newborn , Nuclear Proteins/genetics , Intellectual Disability/genetics , Craniofacial Abnormalities/genetics , Craniofacial Abnormalities/complications , Clubfoot/genetics , Phenotype , Heart Defects, Congenital/genetics , Heart Defects, Congenital/complications , DegronsABSTRACT
OBJECTIVE: To investigate the failure of treatment with chloroquine in Yunnan in order to help formulate adequate antimalarial drug policy. METHODS: A World Health Organization 28-day in vivo test on therapeutic response for uncomplicated falciparum malaria in area with low or moderate transmission was adopted. Patients of age > or = 6 months old were admitted without limitation in density of parasitaemia and body temperature. Clinical and parasitological observation was conducted for patients on day 0, 1, 2, 3, 4, 7, 14, 21, 28 and 35. RESULTS: Of 62 patients identified as malaria cases infected by Plasmodium falciparum only, Plasmodium vivax only or by both species, 52 cases infected by Plasmodium falciparum only were included in the study. The overall treatment failure rate was 40.7%, with early treatment failure (ETF) rate of 1.8% and late treatment failure rate (LTF) of 38.9%. CONCLUSION: The treatment failure rate was much higher than the rate of 25% recommended by WHO. It is suggested that use of single chloroquine should be stopped in the treatment of falciparum malaria cases in such area. No relationship was found between the failure rate and the density of malaria parasites.
