GM2-gangliosidosis, type I (Tay – Sachs disease) in the pediatrician practice

Background. GM2-gangliosidosis, type I (Tay-Sachs disease) is rare hereditary disease caused by mutations in the HEXA gene encoding the alpha subunit of lysosomal hexosaminidase A. It leads to accumulation of GM2-ganglioside in lysosomes and cell death. The major clinical signs of this disease are regression of motor and psychoverbal skills, progressive macrocephaly, diffuse muscle hypotension, convulsive disorder. Almost all patients with this disease have the “cherry red spot” symptom on the fundus of the eye.Clinical case description. We show clinical description of the patient with disease manifested with the lesion of visual analyzer. The child was sent for geneticist’s consultation due to revealed ophthalmic picture of the “cherry red spot” symptom on the fundus of the eye. Molecular genetic testing has revealed in the patient c.1274_1278 dupTATC (CI 880091) mutation in homozygous state in HEXA gene.Concllusion. Differential diagnosis of this disease should be performed with other diseases from the group of inherited metabolic diseases associated with early regression of psychomotor skills, progressive vision loss, “cherry red spot” symptom on the fundus of the eye and convulsive disorder

Whole exome sequencing reveals a homozygous nonsense mutation in HEXA gene leading to Tay-Sachs disease in Saudi Family

Objective: To study the causative variants in affected member of a Saudi family with Tay-Sachs disorder. This disorder includes paralysis, decreasing in attentiveness, seizures, blindness, motor deterioration progresses rapidly leading to a completely unresponsive state and a cherry-red spot visible on the eye. Methods: Whole exome sequencing (WES) and Sanger sequencing was performed to study the variant leading to the disease. Results: WES data analysis and Sanger sequencing validation, identifies a homozygous nonsense mutation c.1177C>T, p.Arg393Ter as a result in protein change. This mutation was also studied in 100 unrelated healthy controls. Conclusions: We detected homozygous mutation in HEXA gene that may lead to cause Tay-Sachs disorder. Moreover, explain the possibility that HEXA gene may play important role for multiple aspects of normal human neurodevelopment. doi: https://doi.org/10.12669/pjms.36.6.2579 How to cite this:Naseer MI, Abdulkareem AA, Jan MM, Chaudhary AG, Al-Qahtani MH. Whole exome sequencing reveals a homozygous nonsense mutation in HEXA gene leading to Tay-Sachs disease in Saudi Family. Pak J Med Sci. 2020;36(6):---------. doi: https://doi.org/10.12669/pjms.36.6.2579 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.