Özlem Akgün Doğan

Effects of freezing on the bactericidal activity of human milk.

Objectives: Storage of human milk by freezing has been recommended for long-term storage. The present study analyzed the bactericidal activity of human milk on Escherichia coli and Pseudomonas aeruginosa and determined the changes in bactericidal activity following freezing at −20°C and −80°C for 1 month and 3 months. Methods: Forty-eight milk samples were collected from 48 lactating mothers. Each sample was divided into 10 aliquots. Two of the samples were processed immediately and the others were stored at both −20°C and −80°C until analysis after 1 month and 3 months of freezing. Results: All of the fresh milk samples showed bactericidal activity against E coli and P aeruginosa. Freezing at −20°C for 1 month did not cause statistically significant alteration in bactericidal activity (P > 0.017), whereas storage for 3 months lowered the degree of bactericidal activity significantly (P < 0.017) against E coli. Bactericidal activity was protected when the samples were stored at −80°C. There was no statistically significant difference in the bactericidal activity of human milk against E coli between freezing at −20°C and −80°C for 1 month (P > 0.017); however, when milk was stored for 3 months, −80°C was significantly more protective (P < 0.017). Freezing at −20°C and −80°C for 1 month and 3 months did not cause any significant change in bactericidal activity against P aeruginosa (P > 0.05). Conclusions: Storage by freezing at −80°C is more appropriate to keep bactericidal capacity of stored human milk >1 month if affordable and available, especially in intensive care settings.

HERC1 mutations in idiopathic intellectual disability

HERC1 is a member of HERC protein family of ubiquitin ligases and is a negative regulator of the mTOR pathway. It is also a guanine nucleotide exchange factor for ARF and Rab family GTPases. Biallelic mutations in HERC1 were recently shown to cause a human phenotype with overgrowth and intellectual disability as main features. Herein we describe clinical features in another patient with homozygous novel mutation in HERC1. Moderate to severe intellectual disability, hypotonia, macrocephaly, tall stature, and facial features appear as main clinical features of the condition. Kyphoscoliosis and seizures frequently accompany and autistic features might be another feature as recent studies also implicate. HERC1 mutations should be considered in differential diagnosis of severe intellectual disability and behavioural problems, particularly in patients testing negative for fragile X and KANSL1 mutations.

Effect of New Breakpoints Proposed by Clinical and Laboratory Standards Institute in 2008 for Evaluating Penicillin Resistance of Streptococcus pneumoniae in a Turkish University Hospital

Clinical and Laboratory Standards Institute changed penicillin susceptibility breakpoints for Streptococcus pneumoniae in 2008. After reevaluation with new breakpoints, resistance rates decreased from 6.1% to 0.5% for nonmeningitis and increased from 6.6% to 33.3% for meningitis isolates in our hospital. This breakpoint modification is expected to reduce the inconsistency between susceptibility results and therapeutic outcomes; however, both the clinical microbiology laboratories and the clinicians should be aware of the change to interpret the susceptibility results.

Homozygous indel mutation in CDH11 as the probable cause of Elsahy–Waters syndrome

Two sisters from a consanguineous couple were seen in genetics department for facial dysmorphic features and glaucoma. They both had broad foreheads, hypertelorism, megalocorneas, thick eyebrows with synophrys, flat malar regions, broad and bulbous noses, and mild prognathism. Both had glaucoma, younger one also had cataracts and phthisis bulbi. Other findings included bilateral partial cutaneous syndactyly of 2nd and 3rd fingers, history of impacted teeth with dentigerous cyst in the elder one, and intellectual disability (mild and borderline). The sisters were considered to have Elsahy–Waters syndrome. In order to elucidate the underlying molecular cause, sisters and their healthy parents were genotyped by SNP arrays, followed by homozygosity mapping. Homozygous regions were further analyzed by exome sequencing in one affected individual. A homozygous indel variant segregating with the condition was detected in CDH11 (c.1116_1117delinsGATCATCAG, p.(Ile372MetfsTer9)), which was then validated by using Sanger sequencing. CDH11 encodes cadherin 11 (osteo‐cadherin) that regulates cell–cell adhesion, cell polarization and migration, as well as osteogenic differentiation. Further experiments revealed that CDH11 expression was decreased in patient‐derived fibroblasts as compared to the heterozygous parent and another healthy donor. Immunostaining showed absence of the protein expression in patient fibroblasts. In addition, cell proliferation rate was slow and osteogenic differentiation potential was delayed. We consider that this study reveals loss‐of‐function mutations in CDH11 as a probable cause of this phenotype. Next generation sequencing in further patients would both prove this gene as causative, and finely delineate this clinical spectrum further contributing in identification of other possibly involved gene(s).

Container type and bactericidal activity of human milk during refrigerated storage.

Background: Refrigeration of human milk has been recommended for its short-term storage. It has been shown that some nutritional, immunological, and bioactive properties and bactericidal activity of human milk can be altered during refrigeration. Pyrex bottles and polyethylene bags are 2 commonly used containers for human milk storage. Objective: The aim of this study was to compare the association between storage container type on the bactericidal activity of human milk for different durations of refrigeration (fresh, and at 24 and 48 hours). Methods: Forty-four samples of human milk were collected from 22 lactating mothers. Two samples of breast milk (approximately 10 mL each) were obtained by manual expression from each mother. One was collected directly into sterile Pyrex bottles and the other into polyethylene bags. One mL of human milk from each container was processed immediately after arrival to the laboratory. The remaining human milk was kept in the Pyrex and polyethylene containers at 4°C until analysis at 24 and 48 hours. The bactericidal activity of each sample was studied. A strain of Escherichia coli ATCC 25922 was used to determine the bactericidal effect of human milk. Results: Bactericidal activity was significantly reduced in milk samples stored in polyethylene bags compared to those stored in Pyrex bottles when milk samples were stored at 4°C for 24 and 48 hours (P < .05). Conclusion: Short-term storage of human milk in Pyrex bottles is more appropriate than polyethylene bags for preserving its bactericidal activity against E coli.

In vitro activities of antifungal drugs against environmental Exophiala isolates and review of the literature

Exophiala is a genus of black fungi isolated worldwide from environmental and clinical specimens. Data on antifungal susceptibility of Exophiala isolates are limited and the methodology on susceptibility testing is not yet standardised. In this study, we investigated in vitro antifungal susceptibilities of environmental Exophiala isolates. A total of 87 Exophiala isolated from dishwashers or railway ties were included. A CLSI M38‐A2 microdilution method with modifications was used to determine antifungal susceptibility for fluconazole, voriconazole, posaconazole, itraconazole, amphotericin B and terbinafine. Minimum inhibitory concentration (MIC) values were determined visually at 48 hours, 72 hours and 96 hours. MIC‐0 endpoint (complete inhibition of growth) was used for amphotericin B and azoles, except fluconazole, for which MIC‐2 endpoint (~50% inhibition compared to growth control) was used. Both MIC‐0 and MIC‐1 (~80% inhibition compared to growth control) results were analysed for terbinafine to enable comparison with previous studies. Fungal growth was sufficient for determination of MICs at 48 hours for all isolates except two Exophiala dermatitidis strains. At 72 hours, most active antifungal agents according to GM MIC were voriconazole and terbinafine, followed by posaconazole, itraconazole and amphotericin B in rank order of decreasing activity. While amphotericin B displayed adequate in vitro activity despite relatively high MICs, fluconazole showed no meaningful antifungal activity against Exophiala.

Hyperphosphatasia with mental retardation syndrome type 4 In two siblings-expanding the phenotypic and mutational spectrum

Hyperphosphatasia with mental retardation syndrome (HPMRS) (OMIM # 239300), is an autosomal recessive disease with phenotypic variability, ranging from mild nonsyndromic intellectual disability to syndromic form with severe intellectual disability, seizures, elevated alkaline phosphatase, brachytelephalangy and facial dysmorphism, Six subgroups of HPMRS were defined in which pathogenic mutations affect genes involved in either synthesis or remodeling of the anchor proteins. Among these, PGAP3 mutations are associated with HPMRS type 4. We report two siblings with a novel homozygous variant in PGAP3 expanding both the phenotypic findings and the mutational spectrum of HPMRS type 4. Developmental delay, hypotonia, facial dysmorphism were the consistent findings with HPMRS in our patients. Large anterior fontanel size, gum hypertrophy, pes equinovarus, concentric ventricle hypertrophy, frontoparietal atrophy and dysphagia were the findings of our patients that have been reported for the first time in this syndrome. Although there is an extensive list of differential diagnoses in patients with developmental delay and hypotonia, the recognizable pattern of facial features, parental consanguinity and mild to moderate serum ALP elevation should be sufficiently suggestive of HPMRS type 4.

A Diagnosis to Consider in an Adult Patient with Facial Features and Intellectual Disability: Williams Syndrome

Williams syndrome (OMIM #194050) is a rare, well-recognized, multisystemic genetic condition affecting approximately 1/7,500 individuals. There are no marked regional differences in the incidence of Williams syndrome. The syndrome is caused by a hemizygous deletion of approximately 28 genes, including ELN on chromosome 7q11.2. Prenatal-onset growth retardation, distinct facial appearance, cardiovascular abnormalities, and unique hypersocial behavior are among the most common clinical features. Here, we report the case of a patient referred to us with distinct facial features and intellectual disability, who was diagnosed with Williams syndrome at the age of 37 years. Our aim is to increase awareness regarding the diagnostic features and complications of this recognizable syndrome among adult health care providers. Williams syndrome is usually diagnosed during infancy or childhood, but in the absence of classical findings, such as cardiovascular anomalies, hypercalcemia, and cognitive impairment, the diagnosis could be delayed. Due to the multisystemic and progressive nature of the syndrome, accurate diagnosis is critical for appropriate care and screening for the associated morbidities that may affect the patients health and well-being.

Coexistence of Trisomy 13 and SRY (−) XX Ovotesticular Disorder of Sex Development

ABSTRACT Introduction: Ovotesticular disorder of sex development (OT-DSD) is a rare disorder of sexual differentiation characterized by the presence of both testicular and ovarian tissue in an individual and the majority of cases have been reported with 46,XX karyotype. In 46,XX cases, testicular differentiation may occur due to the translocation of SRY to the X chromosome or to an autosome. Case report: Herein, we present a female newborn with a combination of trisomy 13 and SRY (-) XX OT-DSD. Conclusion: Trisomy 13 is a relatively common and well-known chromosomal disorder in which disorders of sexual differentiation are not frequent. In the absence of SRY, overexpression of pro-testis genes, or decreased expression of pro-ovarian/anti-testis genes have been suggested as underlying mechanisms of testicular formation. The findings in this patient were suggestive of an underlying genomic disorder associated with FGF9 and/or SPRY2.

Prenatal and Postnatal Follow-up in Trisomies 13 and 18: A 20-Year Experience in a Tertiary Center

Objective Trisomies 13 and 18 are among the most common autosomal aneuploidies associated with high mortality rates. Conventional management strategies offer to limit interventional support; however, some of the recent studies suggest that intervention does make a difference in terms of survival. Study Design A retrospective cohort study was performed between January 1996 and January 2016, covering all cases with such trisomies. A total of 69 cases were reviewed for clinical aspects, outcome, and management strategies. Results In almost all pregnancies with follow‐up, at least one indication present for invasive testing (54/55). Invasive testing was not performed in 18.5% of such cases. All parents opted for termination in cases with prenatal diagnosis. None of the liveborns had prenatal diagnoses, thus, neonatal resuscitation and intensive care unit admission were not withheld in such infants. Major intervention was done in only one patient with full trisomy 13. Median survival for infants with full trisomies 13 and 18 was 36 and 60 days, respectively. Almost half the patients died within 1 month. Conclusion To which extent the major interventions should be withheld is an issue of debate in managing such infants; however, current approaches are subject to change, given the technological advances.