Aromatic L-Amino acid decarboxylase (AADC) deficiency is a rare neurometabolic disorder due to homozygous or compound heterozygous pathogenic variant of the DDC gene, resulting in low synthesis biogenic amines dopamine, serotonin, epinephrine, and norepinephrine. Most patients had severe expression disease with global developmental delay, early hypotonia, movement disorders such as oculogyric c...

defects in genes for survival motor neuron (smn) and neural apoptosis inhibitory proteins (naip) have been reported associated with spinal muscular atrophy (sma). among the genetic defects, deletions in exons 7 and 8 of smn and exons 4 and 5 of naip were found to be most significant. in the current study, 35 unrelated sma patients including 9 patients with type i, 6 with type ii, 20 with type i...

background: inherited thrombophilic gene polymorphisms have been related to the pathogenesis of venous thromboembolism and its outcomes. considering the scarcity of data on the frequency of the thrombophilic gene polymorphisms in iranian populations, the aim of this study was to assess such polymorphisms in healthy individuals. materials and methods: this cross-sectional study was performed on ...

The Atp7b protein is a copper-transporting ATPase expressed predominantly in the liver and to a lesser extent in most other tissues. Mutations in the ATP7B gene lead to Wilson disease, a copper toxicity disorder characterized by dramatic build-up of intracellular hepatic copper with subsequent hepatic and neuro-logical abnormalities. Using homologous recombination to disrupt the normal translat...

Resistance to thyroid hormone β (RTHβ) due to homozygous THRB defects is exceptionally rare, with only five kindreds reported worldwide. Cardiac dysfunction, which can be life-threatening, is recognized in the disorder. Here we describe the clinical, metabolic, ophthalmic, and cardiac findings in a 9-year-old boy harboring a biallelic THRB mutation (R243Q), along with biochemical, physiologic, ...

A Mexican family with partial congenital nephrogenic diabetes insipidus (NDI) that resulted from a mutation in the aquaporin-2 water channel (AQP2) was characterized, and the source of this rare mutation was traced to the family's town of origin in Mexico. Affected individuals with profound polyuria and polydipsia were homozygous for an autosomal recessive missense V168M mutation in the AQP2 ge...

KEY CLINICAL MESSAGE Cockayne syndrome (CS) is a rare autosomal recessive genetic disease characterized by growth failure and progressive neurological degeneration. Here we report a mild form of CS patient who was homozygous for the C526T transition resulting in a new nonsense mutation, which converts Arg176 to a stop codon.

The vitamin D hormone 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the biologically active form of vitamin D, is essential for an intact mineral metabolism. Using gene targeting, we sought to generate vitamin D receptor (VDR) null mutant mice carrying the reporter gene lacZ driven by the endogenous VDR promoter. Here we show that our gene-targeted mutant mice express a VDR with an intact horm...

Heterozygous germ-line variants of DNA mismatch repair (MMR) genes predispose individuals to hereditary non-polyposis colorectal cancer. Several independent reports have shown that individuals constitutionally homozygous for MMR allelic variants develop early onset hematological malignancies often associated to features of neurofibromatosis type 1 (NF1) syndrome. The genetic mechanism of NF1 as...

PURPOSE To identify the genetic defects underlying retinitis pigmentosa (RP) in Pakistani families. METHODS Genome-wide high-density single-nucleotide-polymorphism microarray analysis was performed using the DNA of nine affected individuals from two large families with multiple consanguineous marriages. Data were analyzed to identify homozygous regions that are shared by affected sibs in each...