Arthrogryposis is a rare inherited condition characterized by multiple joint contractures that limit the movement in one or more joints, leading to decreased flexibility. This condition can affect joints across the body including elbows, shoulders, wrists, knees, hips, and fingers. This study describes four different families having hallmark features of arthrogryposis. The whole-exome sequencing followed by Sanger sequencing was performed for all the families using standard methods. Whole-exome sequencing revealed three novel variants and one already reported variant in four different genes. In family A, we identified an already reported homozygous variant (c.834delG; p.Ser279Alafs*191) in exon 8 of the LGI4 gene (NM_139284.3). Family B revealed a potentially causative novel homozygous variant (c.2102C>T; p.Pro701Leu) in exon 16 of the ECEL1 gene (NM_004826.4), whereas in family C we identified a novel homozygous variant (c.4244_4245del; p.Thr1415Serfs*10) in exon 7 of the PIEZO2 gene (NM_001378183.1), and an already reported homozygous deletion (exons 1–10 deletion) in the CNTNAP1 gene (NM_003632.3) was identified in family D. Our results confirm the involvement of these genes in the formation of multisystemic contractures in humans and extend the mutation and clinical spectrum of four distinct forms of arthrogryposis. Arthrogryposis involves multiple joint contractures present at birth, affecting both upper and lower extremities. This study investigates the genetic underpinnings of arthrogryposis in four unrelated Saudi families, revealing disease-causing variants in the LGI4, ECEL1, PIEZO2, and CNTNAP1 genes. Researchers conducted whole-exome sequencing to identify these variants, followed by Sanger sequencing for confirmation. In family A, a frameshift variant in LGI4 was linked to neurogenic arthrogryposis, whereas family B showed a novel missense variant in ECEL1 associated with distal arthrogryposis. Family C had a frameshift variant in PIEZO2, and family D had a deletion in CNTNAP1, causing lethal congenital contracture syndrome. These findings highlight the diverse genetic causes of arthrogryposis and underscore the importance of genetic testing for accurate diagnosis and management. Future research should focus on comprehensive neuro-ophthalmologic evaluations and multidisciplinary care approaches to improve patient outcomes. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
Dyschromatosis symmetrica hereditaria is an autosomal dominant genodermatosis. We report a Vietnamese child with mottled hyperpigmented and hypopigmented macules on the dorsal hands and feet. Genetic testing identified a heterozygous ADAR nonsense variant, c.1944C>A (p.(Tyr648Ter)), also present in his mother and classified as likely pathogenic. To our knowledge, this variant has not previously been reported, and this is one of the few molecularly confirmed Dyschromatosis symmetrica hereditaria cases reported in Vietnam.
Down syndrome (DS) is the most prevalent chromosomal disorder worldwide and is primarily caused by chromosome 21 nondisjunction (Ch21 NDJ). Categorizing trisomy 21 cases by parental origin allows a more precise assessment of maternal age (MA) as a DS risk factor. This study aimed to investigate the association between MA and parental allele transmission patterns at the D21S11 locus in individuals with DS. A familial-based study was conducted by collecting blood samples from 55 DS Libyan families, categorizing into two groups based on MA (<35 years and ≥35 years). Short tandem repeat analysis of D21S11 marker on Ch21 was used to trace allelic transmission from parents to offspring. The parental NDJ errors were traceable in 24 (58.5%) of 41 informative families, with maternal and paternal NDJ errors accounting for 20/24 (83.3%) and 4/24 (16.7%), respectively. Given the limited traceability rate, this investigation should be considered a preliminary study. Among the 24 informative cases, maternal-origin trisomy accounted for 8 of 10 cases (80.0%) in mothers aged <35 years and 12 of 14 cases (85.7%) in mothers aged ≥35 years. The present results suggest that MA may be associated with the distribution of trisomy 21 based on D21S11 parental allele transmission patterns; however, no statistically significant association was detected in the present cohort (P = 0.563). Although additional Ch21 markers are needed, this study provides preliminary insights into MA-related patterns of allele transmission in Libyan individuals with DS. Down syndrome (DS) is a common chromosomal disorder caused by an extra chromosome 21, often linked to advanced maternal age (MA). This study explores the association between advanced MA and trisomy 21 in Libyan DS cases by analyzing parental allele transmission patterns using the D21S11 marker. Researchers collected blood samples from 55 families and used DNA profiling to determine the parental origin of the extra chromosome. The study found that 83.3% of trisomy 21 cases were of maternal origin, with a higher occurrence in mothers aged 35 and older. However, no significant statistical association was found between MA and the origin of trisomy 21. The study highlights the need for larger sample sizes and additional markers to improve the accuracy of parental-origin analysis. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
Nonketotic hyperglycinemia (NKH) is an autosomal recessive neurometabolic disorder caused predominantly by biallelic GLDC variants. We report on a girl with neonatal-onset NKH harboring compound heterozygous variants in GLDC: the novel missense variant GLDC (NM_000170.3):c.898T>C, p.(Cys300Arg), classified as likely pathogenic, and an intragenic deletion involving exons 12–15. Segregation analysis confirmed that the variants were in trans. To our knowledge, this is the first report of p.(Cys300Arg) in a patient with NKH.
Here we report a mother–son pair with Marfan syndrome carrying a novel FBN1 frameshift variant, which was classified as likely pathogenic. The boy developed benign enlargement of the subarachnoid space, accompanied by subdural hemorrhage and transient intracranial hypertension, and mild motor developmental delay. This case suggests a possible association between connective tissue disorders such as Marfan syndrome and complications occurring in infants with benign enlargement of the subarachnoid space.
