Hermansky–Pudlak syndrome (HPS) is a rare disease inherited in the autosomal recessive mode, including 11 clinical genetic subtypes. They are associated with impaired function of the BLOC protein complex (Biogenesis of Lysosome-related Organelles Complexes), and the subunits of the AP-3 complex (adaptor protein complex). Each has its own clinical features, but they are all characterized by albinism, bleeding disorder, and visual abnormalities. Eleven patients from eight unrelated families with an incoming diagnosis of albinism were examined and novel and previously described genetic variants in HPS1, HPS6, and BLOC1S6 genes (types HPS1, HPS6, and HPS9) were found. To determine the optimal therapy and recommendations for further follow up, it is necessary to consider the entire clinical spectrum and genetic polymorphism of the disease. An interdisciplinary approach, combined with the use of non-routine diagnostic techniques such as RNA analysis, is essential for achieving accurate diagnoses in certain complex cases.

The article presents a clinical case involving a patient with presumptive coexistence of two hereditary disorders, confirmed by molecular genetic analyses. Clinical evaluation of the proband, a 9-year-old girl, revealed features characteristic of Kabuki syndrome, including a typical “Kabuki makeup” facial phenotype, short stature, intracranial hypertension, and diffuse muscular hypotonia. Additional clinical findings included chronic right-sided otitis media, conjunctivitis, recurrent pneumonia, bilateral conductive hearing loss, astigmatism, and primary adenitis. Clinical assessment and molecular genetic testing were performed. High-throughput sequencing identified a previously reported pathogenic heterozygous variant in the KMT2D gene, NM_003482.4:c.15142C>T p.Arg5048Cys, and two known heterozygous variants in the CFTR gene: NM_000492.4:c.1521_1523delCTT p.Phe508del and c.3454G>C p.Asp1152His, classified as pathogenic and of variable clinical significance, respectively. Segregation analysis demonstrated that the KMT2D variant most likely arose in the proband de novo, whereas the CFTR variants were inherited from each of the parents. Notably, the proband’s clinically unaffected elder sister carried the same CFTR genotype. Based on the clinical presentation and molecular genetic findings, the diagnosis of Kabuki syndrome type 1 was conclusively established in the patient. Functional assessment of CFTR demonstrated its preserved function, which did not support a diagnosis of CF or CFTR-related disorders.

Introduction: Newborn screening program enable pre-symptomatic detection patients with severe forms of T and B cell immunodeficiency. Despite the high prevalence of 22q11.2 deletion syndrome, only 1 in 10 patients develop lymphopenia that can be detected by newborn screening program. This report presents a unique familial case of 22q11.2 deletion syndrome and Wiskott-Aldrich syndrome, highlighting the importance genetic counseling and a detailed analysis of the family history. Case Presentation: The article presents a case of the two rare genetic diseases in patients from the same family: 22q11.2 deletion syndrome in one and Wiskott-Aldrich syndrome in the other. Both diseases belong to the group of combined immunodeficiencies with syndromic features and are potentially life-threatening conditions requiring follow-up by a wide range of specialists: immunologists, geneticists, cardiologists, endocrinologists, and medical psychologists. Conclusion: Our work aimed to describe the clinical manifestations, genetic characteristics, and diagnosis of these disorders. It is worth emphasizing that the timely diagnosis of not only 22q11.2 deletion syndrome but also other primary immunodeficiencies in the Russian Federation became possible due to the introduction of extended neonatal screening into widespread practice. For such patients, comprehensive early interventional treatment and follow-up by a wide range of specialists is important to improve prognosis and quality of life.