Variants in HCFC1 and MN1 genes causing intellectual disability in two Pakistani families

• Published in: BMC medical genomics Vol. 17; no. 1; pp. 176 - 9
• Main Authors: Hussain, Syeda Iqra, Muhammad, Nazif, Shah, Shahbaz Ali, Rehman, Adil U, Khan, Sher Alam, Saleha, Shamim, Khan, Yar Muhammad, Muhammad, Noor, Khan, Saadullah, Wasif, Naveed
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.07.2024; BioMed Central; BMC
• Subjects: Analysis; Care and treatment; Child; Child, Preschool; Cognitive ability; Diagnosis; Disability; Disease; DNA sequencing; Exome Sequencing; Female; Genes; Genetic aspects; Genetic diversity; Genetic factors; Genetic testing; Genetic variation; Genomes; Genotype & phenotype; HCFC1 gene; Host Cell Factor C1 - genetics; Humans; Intellectual disabilities; Intellectual disability; Intellectual Disability - genetics; Intelligence; Male; Mental illness; Mental retardation; MN1 gene; MN1 protein; Mutation; Nucleotide sequencing; Pakistan; Palate; Pedigree; Phenotypes; Proteins; Sanger Sequencing; Trans-Activators - genetics; Tumor Suppressor Proteins - genetics; Whole genome sequencing; Young adults; Pakistan; United States > US; Sanger Sequencing; HCFC1 gene; Intellectual disability; MN1 gene; Exome sequencing
• ISSN: 1755-8794; 1755-8794
• DOI: 10.1186/s12920-024-01943-2

Intellectual disability (ID) is a neurodevelopmental condition affecting around 2% of children and young adults worldwide, characterized by deficits in intellectual functioning and adaptive behavior. Genetic factors contribute to the development of ID phenotypes, including mutations and structural changes in chromosomes. Pathogenic variants in the HCFC1 gene cause X-linked mental retardation syndrome, also known as Siderius type X-linked mental retardation. The MN1 gene is necessary for palate development, and mutations in this gene result in a genetic condition called CEBALID syndrome. Exome sequencing was used to identify the disease-causing variants in two affected families, A and B, from various regions of Pakistan. Affected individuals in these two families presented ID, developmental delay, and behavioral abnormalities. The validation and co-segregation analysis of the filtered variant was carried out using Sanger sequencing. In an X-linked family A, a novel hemizygous missense variant (c.5705G > A; p.Ser1902Asn) in the HCFC1 gene (NM_005334.3) was identified, while in family B exome sequencing revealed a heterozygous nonsense variant (c.3680 G > A; p. Trp1227Ter) in exon-1 of the MN1 gene (NM_032581.4). Sanger sequencing confirmed the segregation of these variants with ID in each family. The investigation of two Pakistani families revealed pathogenic genetic variants in the HCFC1 and MN1 genes, which cause ID and expand the mutational spectrum of these genes.