Split-hand/foot malformation 3 resulting from microduplications in 10q24 region in five patients from India.

Split-hand/foot malformation (SHFM) is a genetically heterogeneous congenital limb reduction defect characterized by the deficiencies of central rays of the autopod. Tandem duplications at 10q24 locus account for approximately 20% of all SHFM cases. Here, we report five affected individuals from four unrelated Indian families with SHFM3 caused by microduplication of 10q24 locus showing varied clinical presentations. This report substantiates and extends the current understanding of this rare, multifaceted, and complex condition.

Mosaic variegated aneuploidy syndrome 2 with biallelic novel CEP57 splice site variation in Indian siblings: Expanding the clinical and molecular spectrum.

Mosaic variegated aneuploidy syndrome 2 (MVA2) (MIM# 614114) is a rare autosomal recessive condition caused by biallelic loss of function variants in the CEP57 gene. MVA2 is characterized by a variable phenotype ranging from poor growth to facial dysmorphism, short stature and congenital heart defects. Only 11 families and 5 pathogenic variants of MVA2 have been described so far. Intragenic duplication of 11 nucleotides (c.915_925dup11) in homozygous or compound heterozygous state is the commonest genetic aberration (10/13). We describe the first Indian family with two siblings with a novel homozygous splice site variant (c.382+2T>C) in CEP57. Molecular characterization demonstrated skipping of exon 3 due to the variant with protein modeling predicting subsequent complete loss of function. This is the first report of a splice site variation in CEP57 leading to MVA2.

Asparagine Synthetase deficiency-report of a novel mutation and review of literature.

Asparagine synthetase deficiency is a rare inborn error of metabolism caused by a defect in ASNS, a gene encoding asparagine synthetase. It manifests with a severe neurological phenotype manifesting as severe developmental delay, congenital microcephaly, spasticity and refractory seizures. To date, nineteen patients from twelve unrelated families have been identified. Majority of the mutations are missense and nonsense mutations in homozygous or compound heterozygous state. We add another case from India which harbored a novel homozygous missense variation in exon 11 and compare the current case with previously reported cases.

Minimally invasive autopsy in the evaluation of fetal malformations and stillbirths: A feasibility study.

BACKGROUND: Minimally invasive autopsy (MIA) using post-mortem magnetic resonance imaging with ancillary investigations is reported as accurate as conventional autopsy. This study assesses MIA's feasibility and accuracy compared to conventional autopsy. METHOD: MIA and/or conventional autopsy were performed on malformed fetuses (14-20 weeks gestation) and stillbirths (>20 weeks gestation), with/without malformation. Concordance in diagnostic accuracy (95% confidence interval [CI]) and agreement (Kappa coefficient [k]) were assessed in malformed cases where both MIA and autopsy were conducted. RESULTS: We enrolled 200 cases, including 100 malformed fetuses (<20 weeks) and 100 stillbirths (with/without malformations). Concordance of 97.3% was observed between MIA and autopsy in 156 malformed cases. The overall diagnostic accuracy of MIA was 96.04%. CONCLUSION: While conventional autopsy remains the gold standard, MIA is feasible in tertiary care settings. It can be considered a potential alternative for post-mortem assessment, particularly in settings with limited facility of conventional autopsy and parental refusal.

Identification of a Novel 19-bp Deletion Mutation in LTBP4 Using Exome Sequencing in Two Siblings with Autosomal Recessive Cutis Laxa Type 1C.

Autosomal recessive type I cutis laxa is genetically heterogeneous. Biallelic mutations in latent transforming growth factor ß-binding protein 4 (LTBP4; MIM*604710) lead to type 1C cutis laxa due to nonsense, frameshift, single base pair indels, or duplication mutations. In this report, we describe the first Indian family with cutis laxa as a result of a novel 19 base pair homozygous deletion leading to premature termination of short isoform LTBP-4S.