Aug 2026· American Journal of Medical Genetics. Part A· 0 citations· 10 references
Medicine
Abstract
The EEFSEC gene encodes eukaryotic elongation factor selenocysteine-tRNA-specific, an essential component of the selenoprotein biosynthesis machinery required for normal neurodevelopment. Biallelic EEFSEC variants have recently been associated with a rare autosomal recessive neurodevelopmental disorder with variable neurological severity. Here, we describe a Turkish proband carrying the recurrent homozygous EEFSEC (NM_021937.5) variant c.1169A>C; p.Asp390Ala, together with his younger brother, who was identified with the same homozygous variant through familial testing. The proband presented with intellectual disability, delayed motor and expressive language development, mild hypotonia, subtle dysmorphic features, and self-limited early childhood febrile seizures. Compared with previously reported Turkish patients carrying the same variant, his absence of ocular motor involvement, normal neuroimaging, lack of persistent epileptiform abnormalities, and partial developmental gains suggest a relatively milder neurological presentation. The younger brother was initially identified before overt neurological manifestations and subsequently showed delayed expressive language development during early follow-up. This report provides comparative data on the recurrent EEFSEC p.Asp390Ala variant and highlights the value of familial testing, early molecular diagnosis, and longitudinal developmental monitoring in families with confirmed biallelic EEFSEC variants.
This is the first report of the c.470_471del (p.Leu157ArgfsTer4) variant in a homozygous state, providing novel insights into genotype–phenotype correlations and significantly broaden the known clinical spectrum of METTL23-associated disorders.
Findings support a likely contributory role of FLNA p.Pro1926Ser in a variably expressive neurodevelopmental and multisystem disorder in which epilepsy represents the predominant neurological phenotype.
A. Bombaci, E. Micaglio, Sara Benedetti et al.· Neurological Sciences· 0 citations
Background and Clinical Significance: Sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD) syndrome is a rare autosomal recessive disorder caused by biallelic variants in the TRNT1 gene, which encodes tRNA nucleotidyltransferase 1. The disease typically presents early in life with microcytic anemia, recurrent febrile episodes, developmental delay, and immune dysfunction. Because of its rarity and variable clinical expression, diagnosis may be challenging, and broad genetic testing can identify additional variants whose clinical significance requires careful interpretation. Case Presentation: We report a 4-month-old male infant with recurrent febrile episodes, severe recurrent microcytic anemia, recurrent infections, mild psychomotor developmental delay, and multisystem involvement. Genetic analysis identified two heterozygous TRNT1 variants inherited from different parents and confirmed to be in trans: a maternally inherited pathogenic frameshift variant, c.428_431del, p.(Asp143Glyfs12), and a paternally inherited missense variant, c.1246A>G, p.(Lys416Glu), initially classified as a variant of uncertain significance and subsequently interpreted as likely pathogenic in the context of the clinical phenotype and segregation findings. These findings supported the diagnosis of TRNT1-related SIFD syndrome. An additional heterozygous pathogenic C7 variant, c.633_643del, p.(Ser212Hisfs4), was identified. No second pathogenic C7 allele was detected, and functional complement testing was not performed; therefore, complement component 7 deficiency could not be established. Conclusions: This case highlights the importance of early genetic evaluation in infants with recurrent fever, microcytic anemia, immune abnormalities, and multisystem involvement. It also emphasizes the need for cautious interpretation of additional monoallelic pathogenic variants detected by broad genetic panels when functional confirmation and a compatible inheritance pattern are lacking.
I. Jugănaru, Adriana Cojocaru, Andreea Grigoriță et al.· Diagnostics· 0 citations
This study expands the clinical, genetic, and molecular spectrum of EZH1-associated neurodevelopmental disorders by demonstrating that reduced EZH1 expression is consistent with a loss-of-function disease mechanism.
Mohamed Baity, Khalid K Alharbi, Eman Alobeid et al.· International Journal of Mol...· 0 citations
This case expands the molecular spectrum of KBG syndrome and highlights the importance of genomic testing in children presenting with developmental delay, learning difficulties, and subtle dysmorphic features, particularly when the diagnosis remains uncertain during early childhood.
