Coexistence of Bloom Syndrome and Kostmann Disease and a Novel Mutation.

Bloom syndrome (BS) is a rare autosomal recessive inherited disorder. Patients with BS have photosensitivity, telangiectatic facial erythema, and stunted growth. They usually have mild microcephaly, and distinctive facial features such as a narrow, slender face, micrognathism, and a prominent nose. Kostmann disease (KD) is a subgroup of severe congenital neutropenias. The diagnosis of severe congenital neutropenia is based on clinical symptoms, bone marrow findings, and genetic mutation. Here, we report a female patient with a triangular face, nasal prominence, and protruding ears presenting with recurrent infections and severe neutropenia. Molecular genetic testing revealed a compound heterozygous variant in the HCLS-1-associated protein X-1 gene [(c.130_131insA) p.(trp44*), c.430 dup(p.Val144fs)] and a new homozygous variant in Bloom Syndrome RecQ like helicase gene [c.2074+2T>C p.(?)]. She was diagnosed with both BS and KD. To the best of our knowledge, this is the first case of coexisting BS and KD in a patient ever reported.

Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study.

BACKGROUND: Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. METHODS: In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RESULTS: Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively. CONCLUSION: Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients.

Lathosterolosis: a rare cholesterol metabolism disorder with a wide range of clinical variability.

OBJECTIVES: Lathosterolosis is a rare autosomal recessive congenital disease that occurs due to homozygous or compound heterozygous mutations in the sterol C5-desaturase (SC5D) gene. We report a male patient with biallelic missense variant detected in the SC5D gene. CASE PRESENTATION: An eight-month-old male patient was referred to the department of paediatric neurology for status epilepticus. He had no remarkable dysmorphic features except micrognathia, ptotic ear and thin-stranded hair. Laboratory tests revealed an alanine aminotransferase level of 502 IU/L and an aspartate aminotransferase level of 279 IU/L; other biochemical test results were normal. The brain MRI revealed atrophic changes in both hemispheres. A decrease in the volume of brain stem and thin corpus callosum were noticeable. Whole exome sequencing was performed because of consanguineous marriage and sibling death in his medical history, and the encountered features were consistent with suspected neurometabolic disease in the cranial imaging and the presence of borderline psychomotor retardation. A biallelic missense variant, c.656T>C p.(Leu219Ser), was identified in the SC5D gene. CONCLUSIONS: Lathosterolosis is a rare cholesterol metabolism disorder and can be presented with a wide range of clinical features by newly reported cases. Lathosterolosis should be considered in cases with cataracts, delayed neuromotor developmental milestones and high levels of liver enzymes.

A New Variant of the IER3IP1 Gene: The First Case of Microcephaly, Epilepsy, and Diabetes Syndrome 1 from Turkey.

Microcephaly, Epilepsy, and Diabetes Syndrome 1 (MEDS1) is a rare autosomal recessive disorder and caused by defects in the IER3IP1 (Immediate Early Response 3 Interacting Protein 1) gene. Only 9 cases have been described in the literature. MEDS1 manifests as microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes. A simplified gyral pattern has been described in all cases reported to the date. Diagnosis is made by demonstration of specific mutations in the IER3IP1 gene. In this study, we present an additional case of a patient with MEDS1 who is homozygous for the c.53C >T p.(Ala18Val) variant. The case, the first to be reported from Turkey, differs from other cases due to the absence of a typical simplified gyral pattern on early brain MRI, the late onset of diabetes, and the presence of a new genetic variant. The triad of microcephaly, generalized seizures and permanent neonatal diabetes should prompt screening for mutations in IER3IP1.