A family with interleukin-17 receptor A deficiency: a case report and review of the literature.

BACKGROUND: Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections of the skin, nail, oral, and genital mucosa with Candida species, mainly Candida albicans. In a single patient, the first genetic etiology of isolated CMC autosomal recessive interleukin-17 receptor A (IL-17RA) deficiency was reported in 2011. CASE: We report four patients with CMC who displayed autosomal recessive IL-17RA deficiency. The patients were from the same family, and their ages were 11, 13, 36, and 37 years. They all had their first CMC episode by six months of age. All patients manifested staphylococcal skin disease. We documented high IgG levels in the patients. In addition, we found the coexistence of hiatal hernia, hyperthyroidism, and asthma in our patients. CONCLUSIONS: Recent studies have provided new information on the heredity, clinical course, and prognosis of IL-17RA deficiency. However, further studies are needed to reveal the full picture of this congenital disorder.

Distinct Autism Spectrum Disorder Phenotype and Hand-Flapping Stereotypes: Two Siblings with Novel Homozygous Mutation in TRAPPC9 Gene and Literature Review.

Objective: Pathogenic mutations of the TRAPPC9 gene are the rare genetic causes of autosomal recessive intellectual disability (ID). There are several features that are not fully penetrant such as microcephaly, dysmorphic facial features, obesity, autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and brain abnormalities in TRAPPC9 mutations. Methods: We performed whole-exome sequencing to evaluate 2 Turkish siblings with ASD and ID born to healthy and consanguineous parents. Parental samples were also analyzed, specifically targeting variants detected in these patients. Results: We present a novel homozygous mutation in the TRAPPC9 gene, c.484G>T (p.Glu162Ter). Additionally, we aim to provide a more comprehensive understanding of the clinical features of a novel homozygous TRAPPC9 mutation. In addition to ID, the siblings in this report suffered from ASD and specific stereotypes as hand-flapping behavior. Conclusion: Although there are inconsistencies in the presentation of ASD in TRAPPC9 mutations, repetitive behaviors (hand-flapping) were typical in our cases and several previous reports. The current mutation was described to cause a homozygous premature termination codon that resulted in the absence of the TRAPPC9 protein. We suggest that TRAPPC9 mutations are not only related to ID but also to ASD and hand-flapping behaviors.

Clinical, biochemical and genotypical characteristics in biotinidase deficiency.

OBJECTIVES: Hypotonia, lethargy, eczema, alopecia, conjunctivitis, ataxia, hearing loss, optic atrophy, cognitive retardation, and seizures can occur in patients with biotinidase deficiency, and it is inherited as autosomal recessive. The aim of this study was to evaluate the cases followed up with the diagnosis of biotinidase deficiency in our unit, in terms of clinical, biochemical and genetic analyses. METHODS: A total of 112 cases followed up in our centre with the diagnosis of biotinidase deficiency between August 2018-September 2020 were included in the study. Data were collected retrospectively. RESULTS: A total of 112 cases (55.4% male, mean age: 2.2 ± 2.8 years) diagnosed with biotinidase deficiency were evaluated. Diagnoses were made by newborn screening in 90.2% of the cases, by family screening in 4.5%, and by investigating symptoms in 5.4%. The most frequently (27.5%) detected mutations were c.1330G>C (p.D444H)/c.1330G>C (p.D444H) homozygous mutation, followed by (13.0%) c.1330G>C (p.D444H)/c.470G>A (p.R157H) compound heterozygous mutation, and (13.0%) c.470G>A (p.R157H)/c.470G>A (p.R157H) homozygous mutation. Biotinidase enzyme levels were found to be higher in patients with the p.D444H homozygous mutation than patients with other mutations. Biotin treatment was started in all patients with enzyme deficiency. CONCLUSIONS: Since the treatment is inexpensive and easily available, it is vital to detect this disease before symptom onset, especially findings related to the central nervous system, hearing and vision loss. In patients diagnosed with enzyme deficiency, the diagnosis should be definitively confirmed by genetic analysis.

The Vitamin D Receptor Gene Polymorphisms in Asthmatic Children: A Case-Control Study.

Background: The association between vitamin D receptor (VDR) polymorphisms and the risk of asthma remains unclear. This study aimed to investigate the effect of VDR gene polymorphisms and VDR mRNA expression levels on respiratory function, nitric oxide levels in expiratory air, and serum vitamin D levels in children with asthma. Materials and Methods: The study included 80 healthy children (control group) and 100 asthmatic children (asthma group) between the age of 5 and 18 years. The VDR genotypes (ApaI, TaqI, and FokI) and VDR mRNA levels were determined in all groups. Results: There was no statistically significant difference in vitamin D levels between the asthma group and the control group (P > 0.05). A significant association was found between both genotype (CC) of the TaqI polymorphism [odds ratio (OR) = 0.2, 95% confidence interval (CI) (0.07-0.5), P = 0.003] and genotype (CA) of ApaI polymorphisms [OR = 0.2, 95% CI (0.07-0.8), P = 0.02], and asthma risk. In addition, when single-nucleotide polymorphism allelic frequencies between asthma and control groups were compared there is no significant association (P > 0.05). When compared to control group, VDR mRNA expression in asthma group decreased in genotypes CC and CA of ApaI and in genotypes TT and TC of TaqI (P < 0.05). Conclusion: The results provide supporting evidence for an association between TaqI and ApaI polymorphisms and asthma susceptibility.

A case of Riley Ruvalcaba syndrome with a novel PTEN mutation accompanied by diffuse testicular microlithiasis and precocious puberty.

BACKGROUND: Bannayan Riley Ruvalcaba syndrome (BRRS) is exceedingly rare, with only about 50 reported cases to date. CASE PRESENTATION: We report a patient with hypoglycemia, precocious puberty and diffuse testicular microlithiasis accompanying BRRS, and think that this case is important in the light of a newly identified mutation in the PTEN gene. CONCLUSIONS: Close attention must be paid in terms of PTEN mutations in cases of macrocephaly and accompanying neurological and dermatological findings.

A rare cause of neonatal hypoglycemia in two siblings: TBX19 gene mutation.

Congenital isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rarely seen disease characterized by low serum ACTH and cortisol levels accompanied by normal levels of the other anterior pituitary hormones. In these patients, severe hypoglycemia, convulsions, and prolonged cholestatic jaundice are expected findings in the neonatal period. In this paper, we present two siblings with TBX19 gene mutation. The first case was investigated at the age of 2 months for severe hypoglycemia, recurrent convulsions, and prolonged cholestatic jaundice persisting since the neonatal period. The second sibling presented with hypoglycemia in the neonatal period. In both cases, baseline cortisol and ACTH levels were low and cortisol response to the low-dose ACTH test was inadequate, while all other anterior pituitary hormones were normal. Thus, IAD was suspected. Genetic analysis of the TBX19 gene was performed. Both cases were homozygous for c.856 C>T (p.R286*), and hydrocortisone treatment was initiated. The first patient did not attend the clinic regularly. On attendance at another hospital, hydrocortisone treatment was discontinued and antiepileptic treatment was initiated because of suspected epilepsy. This led to developmental delay, measured with the Denver Developmental Screening Test II (DDST-II), because of cessation of the hydrocortisone therapy. The second sibling had normal development, as measured with the DDST. In conclusion, TBX19 gene analysis must be performed if adrenal insufficiency is associated with isolated ACTH deficiency. Delay in diagnosis may lead to inappropriate diagnoses, such as epilepsy, and thus inappropriate therapy, which may result in neonatal mortality.

Mandibuloacral dysplasia and LMNA A529V mutation in Turkish patients with severe skeletal changes and absent breast development.

Mandibuloacral dysplasia (MAD) is an autosomal recessive disorder characterized by acroosteolysis (resorption of terminal phalanges), skin changes (hyperpigmentation), clavicular hypoplasia, craniofascial anomalies, a hook nose and prominent eyes, delayed closures of the cranial sutures, lipodystrophy, alopecia, and skeletal anomalies. MAD patients are classified according to lipodystrophy patterns: type A and type B. The vast majority of MAD cases are caused by LMNA gene mutations. MAD patients with type A lipodystrophy (MADA) have been reported to have LMNA R527H, A529V, or A529T mutations. In this report, we describe two MADA patients with progressive skeletal changes, absent breast development, and cataract in addition to the classical MAD phenotype. Both patients were found to be homozygous for the Ala529Val mutation of the LMNA gene. Our female patient is the oldest MADA patient (59 years old) who has ever been reported with the LMNA mutation and also the LMNA Ala529Val mutation. This study is the second report on MADA patients with a homozygous Ala529Val mutation.

Chromosomal Translocation t (10;19) (q11.2;q13.4) in an Infertile Male.

Chromosomal rearrangements are usually associated with male factor infertility. We report here a 34-year-old man suffering from primary infertility for 15 years. The cytogenetic analysis and investigation of Y-chromosome microdeletions were performed. A reciprocal balanced translocation t (10;19) (q11.2;q13.4) was found in oligozoospermic infertile men with no Y-chromosome microdeletions. In this case, we aimed to evaluate the 46,XY,t (10;19) (q11.2;q13.4) karyo-type, which was detected through a cytogenetic analysis of a person referred to our genetic laboratory due to primary infertility, in the light of the literature.