Identification and growth features of developmental delay with macrocephaly caused by a novel TRIO variant affecting the second SH3 domain.

Expansion of the allelic and phenotypic spectrum of MED25-related developmental disorder: novel compound heterozygous variants with structural domain implications

Biallelic ABCA13 Loss-of-Function Variants in a Child With Neurodevelopmental Delay: A Case Report.

ABCA13 encodes ATP-binding cassette subfamily A member 13, one of the largest members of the ABC transporter family. Rare ABCA13 variants have been reported in neuropsychiatric and neurodevelopmental phenotypes, including schizophrenia, bipolar disorder, autism spectrum disorder, intellectual disability, and developmental delay; however, the mode of inheritance remains uncertain, and most published cases have focused on heterozygous variants in the context of a possible dominant or susceptibility model. We report a 5-year-old boy with neurodevelopmental delay, skeletal foot deformities, nonspecific dysmorphic features, convergent strabismus, and behavioral abnormalities. Initial genome sequencing analysis was nondiagnostic. Reanalysis after 6 months identified two rare predicted loss-of-function variants in ABCA13 in trans: c.2510del, p.(Leu837TyrfsTer21), a frameshift variant, and c.12064C>T, p.(Arg4022Ter), a nonsense variant previously reported in a patient with unexplained intellectual disability. The identification of compound heterozygous predicted loss-of-function variants supports the possibility that biallelic disruption of ABCA13 may contribute to neurodevelopmental disease, whereas previously reported heterozygous variants may represent incompletely penetrant risk alleles, susceptibility factors, or candidate findings rather than fully penetrant dominant causes. This case expands the emerging clinical and genetic spectrum associated with ABCA13 and supports further evaluation of a recessive model in patients with intellectual disability and neurodevelopmental delay.

TTC14 dysfunction contributing to microcephaly and lissencephaly spectrum features through protein mislocalization and impaired RNA processing

Tetratricopeptide Repeat Domain 14 plays a crucial role in RNA metabolism during neurodevelopment, and that the p.His30Arg variant impairs its function, possibly leading to a neurodevelopmental disorder within the lissencephaly spectrum.

Delineation of a Novel Mirror Syndrome: NFIC Variants Cause Syndromic Intellectual Disability With Macrocephaly

NFIC-related disorder represents a novel neurodevelopmental syndrome characterized by intellectual disability and macrocephaly, highlighting the importance of NFIC dosage supporting a mirror-syndrome model.

Genotype-phenotypic correlation in a Chinese patient with isolated lissencephaly sequence caused by 17p13.3p13.2 chromosomal microdeletion: a 6-year follow-up study

Isolated lissencephaly sequence (ILS) is a severe neurodevelopmental disorder associated with 17p13.3 microdeletion. This 6-year longitudinal study aimed to systematically characterize physical and neurodevelopmental trajectories of a Chinese ILS patient and offer evidence for early diagnosis and clinical intervention. From April 2021 to April 2026, a child with severe developmental delay and his family members (parents and elder brother) were recruited in Lianyungang, eastern China. Trio whole-exome sequencing (trio-WES) and copy number variation sequencing (CNV-seq) were used to identify the pathogenic variant. Serial physical growth and neurodevelopmental assessments were conducted during the 6-year longitudinal follow-up. Bioinformatics analysis was used to explore potential molecular pathogenic mechanisms. A de novo 2.06 Mb heterozygous deletion at 17p13.3p13.2 (chr17:1707883_3765621del, GRCh37) was identified in the proband, which included PAFAH1B1 but spared YWHAE and CRK . Longitudinal data showed a progressive decline in both height and weight. Height Z score decreased from −0.37 at 2 months to −1.92 at 57 months. Weight Z score decreased from −1.25 at 2 months to −1.79 at 57 months. Gesell developmental quotients (DQ) showed significant progressive declines in five domains with a decelerating trajectory: adaptive behavior (B 2 = 0.019, 95% CI : 0.002–0.036, R Q 2 = 0.978), gross motor (B 2 = 0.013, 95% CI : -0.004 – 0.030, R Q 2 = 0.944), fine motor (B 2 = 0.017, 95% CI : -0.012 – 0.047, R Q 2 = 0.870), language (B 2 = 0.021, 95% CI : -0.006 – 0.049, R Q 2 = 0.905), personal social behavior (B 2 = 0.020, 95% CI : -0.014 - 0.054, R Q 2 = 0.847). Bioinformatics analysis confirmed that haploinsufficiency of the PAFAH1B1 gene was the primary pathogenic cause. Furthermore, genes in the deleted region were significantly enriched in olfactory perception and calcium ion transmembrane transport pathways. This study reports a 6-year longitudinal follow-up of ILS in a Chinese patient. PAFAH1B1 haploinsufficiency causes the core lissencephaly phenotype, while co-deletion of olfactory and calcium-regulatory genes may exert synergistic effects. These findings expand the phenotypic spectrum of ILS in Chinese populations and provide insights for mechanistic studies and genetic counseling.

Phenotypic Expansion of PPP1R12A-Related Syndrome: A Novel Splicing Variant Associated with Hearing Loss and Inner Ear Malformations

The findings suggest that PPP1R12A-related disorders may exhibit a broader phenotypic variability than previously recognized and it is proposed that HL and inner ear malformations may represent novel features associated with this clinical spectrum.