HIDEA syndrome is caused by biallelic, pathogenic, rare or founder P4HTM variants impacting the active site or the overall stability of the P4H-TM protein

HIDEA syndrome is caused by biallelic pathogenic variants in P4HTM. The phenotype is characterized by muscular and central hypotonia, hypoventilation including obstructive and central sleep apneas, intellectual disability, dysautonomia, epilepsy, eye abnormalities, and an increased tendency to develop respiratory distress during pneumonia. Here, we report six new patients with HIDEA syndrome caused by five different biallelic P4HTM variants, including three novel variants. We describe two Finnish enriched pathogenic P4HTM variants and demonstrate that these variants are embedded within founder haplotypes. We review the clinical data from all previously published patients with HIDEA and characterize all reported P4HTM pathogenic variants associated with HIDEA in silico. All known pathogenic variants in P4HTM result in either premature stop codons, an intragenic deletion, or amino acid changes that impact the active site or the overall stability of P4H-TM protein. In all cases, normal P4H-TM enzyme function is expected to be lost or severely decreased. This report expands knowledge of the genotypic and phenotypic spectrum of the disease.publishedVersio

A Case of DeSanto-Shinawi Syndrome in Bahrain with a Novel Mutation

DeSanto-Shinawi syndrome is a rare genetic condition caused by loss-of-function mutation in WAC. It is characterized by dysmorphic features, intellectual disability, and behavioral abnormalities. In this case report, we describe the clinical features and genotype of a patient with a novel mutation 1346C > A in WAC. This patient’s dysmorphic features include a prominent forehead, bulbous nasal tip, macroglossia, deep-set eyes, and malar hypoplasia. This patient also showed signs of intellectual disability and behavioral abnormalities such as night terrors. These findings are consistent with those described in earlier reports. Here, we report new findings of epilepsy and recurrent skin infections which had not been reported in prior studies

Infantile systemic hyalinosis: report of a case from Bahrain and review of literature

Background: Infantile systemic hyalinosis (ISH), an allelic form of hyaline fibromatosis syndrome, is a rare fatal autosomal recessive disorder that is caused by mutations in the CMG2/ANTRX2 gene encoding the transmembrane anthrax toxin receptor 2. It has a compound of features due to the accumulation of hyaline material in multiple organs including characteristic skin lesions, joint contractures, persistent diarrhea, and failure to thrive. The resulting severe malnutrition can be the cause of death in early infancy. Due to its rarity and early high fatality rate, timely diagnosis is difficult, and children with ISH may die undiagnosed. Case Presentation: In this report, we describe a 3-year-old female diagnosed with ISH after reviewing her clinical and laboratory workup in Salmaniya Medical Hospital. She was diagnosed with ISH based on the clinical presentation of severe skin lesions, painful joint contractures, and later developed renal tubular acidosis. Her diagnosis was confirmed with skin histopathology and identification of homozygous ANTRX2 mutation, c.652T>C, p.Cys218Arg, and Chr4 (GRCh37): g.80957171A>G. Conclusion: While the clinical outcome of the disease is poor without curative treatment, establishing an early diagnosis of ISH, beginning with clinical suspicion to molecular analysis, is important for accurate management as well as carrier and risk assessment of family members. [JBCGenetics 2020; 3(2.000): 108-112

Variable manifestations in lysinuric protein intolerance: a report of two novel mutations from Bahrain

Background: Lysinuric protein intolerance (LPI) is a metabolic disorder resulting from mutations in the SLC7A7 gene that is inherited in the autosomal recessive pattern. The disease has been described sporadically worldwide, including a few cases from Arab countries. The affected patients typically present with failure to thrive, hepatosplenomegaly, and protein intolerance. Various complications such as autoimmune disorders, infiltrative lung disease, hemophagocytic lymphohistiocytosis (HLH), and neurological manifestations could be noted during the disease course. Methodology: We described patients diagnosed with LPI in Bahrain by reviewing their presentations, complications encountered, genetic variability, and treatment options. Results: Four patients, two males and two females from three families with an age range between 2 and 14 years, were followed. Failure to thrive and HLH were the main presenting features in all patients. Two novel mutations were detected in the SLC7A7 gene. One of them was a homozygous splice-site mutation of c.1429+1G>C., whereas the second mutation was a homozygous missense mutation of c.168T>G p. (Phe56Leu). Lung complications were found in two patients, autoimmunity observed in two patients, gastrointestinal complication presenting as hemorrhagic gastritis in one patient, and neurological complications were seen in one patient. Conclusion: The main presenting feature in all the patients was HLH. Two novel mutations in the SLC7A7 gene were detected. Rheumatological complications were variable within the same family members; moreover, hemorrhagic gastritis was reported in one of the patients as a new possible complication related to the disease. [JBCGenetics 2020; 3(1.000): 7-13

HIDEA syndrome is caused by biallelic, pathogenic, rare or founder P4HTM variants impacting the active site or the overall stability of the P4H-TM protein

Abstract HIDEA syndrome is caused by biallelic pathogenic variants in P4HTM. The phenotype is characterized by muscular and central hypotonia, hypoventilation including obstructive and central sleep apneas, intellectual disability, dysautonomia, epilepsy, eye abnormalities, and an increased tendency to develop respiratory distress during pneumonia. Here, we report six new patients with HIDEA syndrome caused by five different biallelic P4HTM variants, including three novel variants. We describe two Finnish enriched pathogenic P4HTM variants and demonstrate that these variants are embedded within founder haplotypes. We review the clinical data from all previously published patients with HIDEA and characterize all reported P4HTM pathogenic variants associated with HIDEA in silico. All known pathogenic variants in P4HTM result in either premature stop codons, an intragenic deletion, or amino acid changes that impact the active site or the overall stability of P4H-TM protein. In all cases, normal P4H-TM enzyme function is expected to be lost or severely decreased. This report expands knowledge of the genotypic and phenotypic spectrum of the disease