Little is known about the molecular pathogenesis of congenital nephrotic syndrome in association with primary adrenal insufficiency. Most recently, three groups found concurrently the underlying genetic defect in the gene sphingosine-1-phosphate lyase 1 (SGPL1) and called the disease nephrotic syndrome type 14 (NPHS14). In this report we have performed whole-exome sequencing and identified a new homozygous variant in SGPL1, p.Arg340Trp, in a girl with nephrotic syndrome and Addison's disease. Her brother died previously with the same phenotype and hyperpigmentation of the skin. We reviewed the reported cases and concluded that NPHS14 is a clinically recognizable syndrome. The discovery of this syndrome may contribute to the diagnosis and description of additional patients who could benefit from treatment, genetic counseling and screening for related comorbidities. Until now, patients with congenital nephrotic syndrome associated with primary adrenal insufficiency have been treated as having two different diseases; however, the treatment for patients with NPHS14 should be unique, possibly targeting the sphingolipid metabolism.
The increase in the number of infections caused by Candida species and the consequent use of antifungal agents favours an increase of resistant isolates. The aim of this study was to evaluate the antifungal susceptibility of Candida spp. isolates from patients with different systemic predisposing factors to candidosis. Seventy-nine Candida spp. isolates were assayed for in vitro susceptibility to amphotericin B, fluconazole, 5-flucytosine and itraconazole using the technique proposed by the Clinical and Laboratory Standards Institute (CLSI). Four C. albicans, one C. guilliermondii, four C. parapsilosis and two C. tropicalis isolates were resistant to amphotericin B. Only two isolate was resistant to itraconazole. All the isolates tested were susceptible to fluconazole and flucytosine. It could be concluded that the most efficient drugs against the Candida isolates studied were fluconazole and flucytosine and that all of the antifungal agents used in this study were effective against the Candida spp. isolates tested.
Laron's syndrome (LS) is a rare genetic disorder characterized by insensitivity to growth hormone (GH). Up to the present time, over 70 mutations of GH receptor (GHR) gene have been identified leading to GH/insulin-like growth factor type 1 (IGF1) signaling pathway defect. The number of LS patients worldwide is unknown, as many are probably undiagnosed. We report two sibs from a consanguineous family from Minas Gerais, southeastern Brazil. The parents have three children. The older, a 4-years-old girl was 80.2 cm tall (-5.7 SDS height/age), and the youngest sister, aged 3 years, was 73.2 cm tall (-5.82 SDS height/age). Their clinical and biochemical features are typical of LS patients, such as high serum level of GH and low IGF1 concentrations. A homozygous c.1A>T nucleotide substitution in GHR exon 2 in the probands' samples was identified. Their parents and healthy sister are heterozygous for the same variant that abolishes the translation initiation codon of GHR. This mutation has not been reported in Brazilian patients and was previously associated with an LS phenotype in a single 29-year-old Spanish man. In addition to this case report, we summarize the main characteristics and molecular data of the 21 LS Brazilian patients who have been published to date.Patients with LS have characteristic biochemical features, such as high (or normal) serum level of GH and low IGF1 concentration (Laron, 2004;Laron et al., 2012). Clinically it is characterized by dwarfism, obesity, small genitalia in the boys, and severe hypoglycemia. Patients present a typical head configuration, a small face and a protruding forehead, resulting in a saddle nose. Their voices are highpitched and they are sparse haired. Phenotypically they re-
We report on a 16-year-old boy with a maternally inherited ~ 18.3 Mb Xq13.2-q21.31 duplication delimited by aCGH. As previously described in patients with similar duplications, his clinical features included intellectual disability, developmental delay, speech delay, generalized hypotonia, infantile feeding difficulties, self-injurious behavior, short stature and endocrine problems. As additional findings, he presented recurrent seizures and pubertal gynecomastia. His mother was phenotypically normal and had completely skewed inactivation of the duplicated X chromosome, as most female carriers of such duplications. Five previously reported patients with partial Xq duplications presented duplication breakpoints similar to those of our patient. One of them, a fetus with multiple congenital abnormalities, had the same cytogenetic duplication breakpoint. Three of the reported patients shared many features with our proband but the other had some clinical features of the Prader-Willi syndrome. It was suggested that ATRX overexpression could be involved in the major clinical features of patients with partial Xq duplications. We propose that this gene could also be involved with the obesity of the patient with the Prader-Willi-like phenotype. Additionally, we suggest that the PCDH11X gene could be a candidate for our patient's recurrent seizures. In males, the Xq13-q21 duplication should be considered in the differential diagnosis of Prader-Willi syndrome, as previously suggested, and neuromuscular diseases, particularly mitochondriopathies.
Biotinidase deficiency is an autosomal recessive inherited metabolic disorder caused by mutations in the BTD gene. Clinical manifestations can be treated and effectively prevented with pharmacological doses of biotin. Nine novel mutations in BTD are reported in 14 children diagnosed by the newborn screening program in Minas Gerais, Brazil, from June 2013 to December 2017. Serum BTD enzyme activity was determined for all cases and some parents. Two of the mutations are deletions and seven missense mutations located in the exonic region of the BTD gene, mostly in exon 4. Two newborns were profoundly biotinidase‐deficient (one homozygous p.A534V [c.1601C > T] and another, double heterozygous for a novel mutation p.R211S [c.631C > A] co‐inherited with an already described mutation p.T532 M [c.1595C > T]). Two mutations were associated with a partial deficiency of biotinidase (p.F361 V [c.1081 T > G] in two homozygous children, and p.S311 T [c.932G > C] in a compound heterozygous child who co‐inherited a known severe mutation p.Y438X [c.1314 T > A]). The remaining five mutations were found in compound heterozygous children. Hence, a definitive conclusion about the degree of biotinidase deficiency is not possible yet. These results emphasize the importance of sequencing the BTD gene as an important tool to gain a better understanding of the correlation between biochemical phenotype and genotype.
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