Correction: Mutational analysis of <i>ITPR1</i> in a Taiwanese cohort with cerebellar ataxias

Correction: Mutational analysis of <i>ITPR1</i> in a Taiwanese cohort with cerebellar ataxia

The molecular and clinical characteristics of <i>ITPR1</i>-associated autosomal dominant cerebellar ataxias in the literature.

<p>The molecular and clinical characteristics of <i>ITPR1</i>-associated autosomal dominant cerebellar ataxias in the literature.</p

The clinical characteristics of the cases reported in this paper.

<p>The clinical characteristics of the cases reported in this paper.</p

The structure of human IP3R1.

<p>(A) The number 1 ~ 19 represent the amino acid residue substitutions reported as far associating with cerebellar ataxia. The blue rectangle represents the IP3 binding region, the red curve line denotes the coupling/regulatory region, and the yellow cylinders stand for the transmembrane segments. (B) The amino acid sequence of the sixth transmembrane segment of human IP3R1 was annotated by the UniProt. The <i>ITPR1</i> p.V2574A mutation resides in an evolutionarily conserved region, as shown by aligning the amino acid sequences of IP3R1 protein orthologs from various species.</p> <p>Abbreviation: ER: endoplasmic reticulum</p> <p>^#Remarks: All the nucleotide positions and amino acid residues represented here were converted to the reference sequence of NM_001168272 for CDS and NP_001161744 for protein sequence.</p

The pedigree and electropherogram of the patients carrying <i>ITPR1</i> c.7721T>C mutation.

<p>(A) The pedigree of the individuals carrying <i>ITPR1</i> p.V2574A (c.7721T>C) mutation in this study. The proband (II-3) is denoted by an arrow. Filled symbols represent symptomatic members, open symbols indicate unaffected individuals, circles stand for females, squares stand for males, WT/WT indicates wild type, and WT/MT stands for individuals harboring the heterozygous mutation. (B) The electropherograms of the patients (II-3 and III-1) carrying the <i>ITPR1</i> mutation (WT/MT) and a healthy family member (II-1) carrying two alleles of wild type <i>ITPR1</i>. The stars denote the location of the mutation.</p

Bioinformatics analyses of <i>ITPR1</i> missense variants.

<p>Bioinformatics analyses of <i>ITPR1</i> missense variants.</p

Brain MRI of the patients carrying <i>ITPR1</i> mutation.

<p>The neuroimages of II-3 are shown as A1-E1, and her daughter’s images (III-1) are A2-E2. The T1-weighted sagittal view images denote a mild atrophy of the anterior and posterior lobes of the cerebellar vermis (A1 and A2). The T1-weighted axial view images demonstrate a mild atrophy of the cerebellar hemispheres (B1-C1 and B2-C2). The sizes of the pons and cerebellar peduncles are within normal ranges. The fluid-attenuated inversion recovery (FLAIR) axial view image features normal cerebral cortex, basal ganglia and midbrain (D1-E1 and D2-E2).</p

Two novel <i>de novo GARS</i> mutations.

<p>(A) The novel <i>GARS</i> mutations identified in this study, p.Asp146Tyr and p.Met238Arg, with the sense strand electropherogram shown on the top and a limited reading frame depicting the corresponding amino acid substitutions shown below. (B) Pedigrees of the 2 patients harboring the novel <i>GARS</i> mutations. The arrows indicate the probands. “M” represents the <i>GARS</i> mutations and “W” means wild type. (C) The <i>GARS</i> p.Asp146Tyr and p.Met238Arg mutations reside in an evolutionarily conserved region, as shown by aligning the amino acid sequences of glycyl-tRNA synthetase protein (GlyRS) orthologs from various species.</p

Clinical features of the patient harboring the <i>GARS</i> p.Asp146Tyr mutation.

<p>(A) Severe weakness and atrophy of the muscles in the feet and legs, pes planus and (B, C) severe intrinsic hand muscle atrophy with claw hand deformity.</p

Clinical and molecular features of mutations in the <i>GARS</i> gene.

<p>^a C: Catalytic domain; DI: dimer interface; W: WHEP domain; Ins I: Insertion I domain; Ins II: Insertion II domain; Ins III: Insertion III domain; ACBD: anti-codon binding domain</p><p>^b * average age of disease onset</p><p>^c CMT: Charcot-Marie-Tooth disease; SMA: spinal muscular atrophy; dSMA: distal SMA;</p><p>^d AD: autosomal dominant; NA: not available</p><p>Clinical and molecular features of mutations in the <i>GARS</i> gene.</p