scholarly journals A Novel Mutation of the Signal Peptide of the Preproparathyroid Hormone Gene Associated with Autosomal Recessive Familial Isolated Hypoparathyroidism*

1999 ◽  
Vol 84 (10) ◽  
pp. 3792-3796 ◽  
Author(s):  
Thongkum Sunthornthepvarakul ◽  
Sunchai Churesigaew ◽  
Supunnee Ngowngarmratana
Keyword(s):  
Signal Peptide ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Family Members ◽  
Autosomal Recessive Inheritance ◽  
Signal Peptidase ◽  
Normal Position ◽  
Intact Pth ◽  
Amino Acid Signal Peptide ◽  
Amino Acid Signal

Abstract We report a novel mutation of the signal peptide of the prepro-PTH gene associated with autosomal recessive familial isolated hypoparathyroidism. The proposita presented with neonatal hypocalcemic seizures. Serum calcium was 1.5 mmol/L (normal, 2.0–2.5); phosphate was 3.6 mmol/L (normal, 0.9–1.5). She was born to consanguineous parents. A few years later, 2 younger sisters and her niece presented with neonatal hypocalcemic seizures. Their intact PTH levels were undetectable during severe hypocalcemia. Genomic DNA from the proposita was sequenced all exons of the prepro-PTH gene. A replacement of thymine with a cytosine was found in the first nucleotide of position 23 in the 25-amino acid signal peptide. This results in the replacement of the normal Ser (TCG) with a Pro (CCG). Genotyping of family members was carried out by identification of a new MspI site created by the mutation. Only affected family members were homozygous for the mutant allele, whereas the parents were heterozygous, supporting autosomal recessive inheritance. As this mutation is at the− 3 position in the signal peptide of the prepro-PTH gene, we hypothesized that the prepro-PTH mutant might not be cleaved by signal peptidase at the normal position, and it might be degraded in rough endoplasmic reticulum.

scholarly journals Biogenesis of T Pili in Agrobacterium tumefaciens Requires Precise VirB2 Propilin Cleavage and Cyclization

2002 ◽  
Vol 184 (1) ◽  
pp. 327-330 ◽  
Author(s):  
Erh-Min Lai ◽  
Ralf Eisenbrandt ◽  
Markus Kalkum ◽  
Erich Lanka ◽  
Clarence I. Kado
Keyword(s):  
Amino Acid ◽  
Agrobacterium Tumefaciens ◽  
Signal Peptidase ◽  
E Coli ◽  
Amino Acid Peptide ◽  
Pilus Biogenesis ◽  
Amino Acid Signal Peptide ◽  
Peptide Product ◽  
Amino Acid Signal

ABSTRACT VirB2 propilin is processed by the removal of a 47-amino-acid signal peptide to generate a 74-amino-acid peptide product in both Escherichia coli and Agrobacterium tumefaciens. The cleaved VirB2 protein is further cyclized to form the T pilin in A. tumefaciens but not in E. coli. Mutations in the signal peptidase cleavage sequence of VirB2 propilin cause the formation of aberrant T pilin and also severely attenuate virulence. No T pilus was observed in these mutants. The potential role of the exact VirB2 propilin cleavage and cyclization in T pilus biogenesis and virulence is discussed.

A Novel Mutation of HINT1 Gene in an Adolescent Female with Axonal Neuropathy and Neuromyotonia

2020 ◽  
Author(s):  
Bülent Kara ◽  
Sedat Gül ◽  
Ayfer Sakarya Güneş ◽  
Serap Mülayim ◽  
Gözde Yeşil
Keyword(s):  
Genetic Testing ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Axonal Neuropathy ◽  
Gene Mutations ◽  
Autosomal Recessive Inheritance ◽  
Muscle Stiffness ◽  
Adolescent Female ◽  
Recessive Inheritance ◽  
Exome Analysis

Abstract HINT1 gene mutations cause an axonal neuropathy with some specific findings including presence of neuromyotonia, autosomal recessive inheritance, onset in the first decade, and primary motor involvement. We described an 18-year-old female patient who presented to the clinic with gait instability and muscle stiffness. A homozygous novel c.180_181delAT (p.Ser61Profs*8) variant in the HINT1 gene was found by clinical exome analysis. Parents were heterozygous for the same variant. The patient was diagnosed with autosomal recessive axonal neuropathy with neuromyotonia. The presence of neuromyotonia must be evaluated in patients with hereditary axonal neuropathies as this can help the diagnosis prior to genetic testing.

scholarly journals Congenital Polycythemia in Chuvashia

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 2148-2154 ◽  
Author(s):  
Adelina Sergeyeva ◽  
Victor R. Gordeuk ◽  
Yuri N. Tokarev ◽  
Lubomir Sokol ◽  
Jaroslav F. Prchal ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Receptor Gene ◽  
Family Members ◽  
Oxygen Affinity ◽  
Pcr Amplification ◽  
Autosomal Recessive Inheritance ◽  
Erythropoietin Receptor ◽  
Unknown Etiology ◽  
Cell Counts ◽  
White Blood Cell Counts

Abstract Familial and congenital polycythemia, not due to high oxygen affinity hemoglobin or reduced 2,3-diphosphoglycerate in erythrocytes, is common in the Chuvash population of the Russian Federation. Hundreds of individuals appear to be affected in an autosomal recessive pattern. We studied six polycythemic Chuvash patients <20 years of age from unrelated families and 12 first-degree family members. Hemoglobins were markedly elevated in the index subjects (mean ± standard deviation [SD] of 22.6 ± 1.4 g/dL), while platelet and white blood cell counts were normal. Although performed in only three of the index subjects, serum erythropoietin concentrations determined by both radioimmune and functional assays were significantly higher in polycythemic patients compared with first-degree family members with normal hemoglobin concentrations. Southern blot analysis of the Bgl 2 erythropoietin gene polymorphism showed that one polycythemic subject was a heterozygote, suggesting the absence of linkage of polycythemia with the erythropoietin gene, assuming autosomal recessive inheritance. Polymerase chain reaction (PCR) amplification of the GGAA and GA minisatellite polymorphic regions of the erythropoietin receptor gene showed no evidence of linkage of phenotype with this gene. We conclude that Chuvash polycythemia may represent a secondary form of familial and congenital polycythemia of as yet unknown etiology. This condition is the only endemic form of familial and congenital polycythemia described.

scholarly journals Three novel paralogs of the rodent prolactin gene family

2000 ◽  
Vol 166 (1) ◽  
pp. 63-75 ◽  
Author(s):  
G Dai ◽  
D Wang ◽  
B Liu ◽  
JW Kasik ◽  
H Muller ◽  
...  
Keyword(s):  
Amino Acid ◽  
Gene Family ◽  
Signal Peptide ◽  
Glycosylation Site ◽  
New Members ◽  
Acid Protein ◽  
Amino Acid Signal Peptide ◽  
Chorioallantoic Placenta ◽  
Amino Acid Protein ◽  
Amino Acid Signal

The prolactin (PRL) family consists of a collection of genes expressed in the uterus, placenta and anterior pituitary. These cytokines/hormones participate in the control of maternal-fetal adaptations to pregnancy. In this report, we establish the presence of three new members of the PRL family. Novel expressed sequence tags (ESTs) with homology to PRL were isolated from embryonic and placental cDNA libraries. The cDNAs were sequenced and compared with those of other members of the PRL family. The three new cDNAs were assigned to the PRL family on the basis of sequence similarities and were referred to as PRL-like protein-J (PLP-J), PRL-like protein-K (PLP-K) and PRL-like protein-M (PLP-M). Both rat and mouse PLP-J cDNAs were identified. Rat PLP-J cDNA encodes for a predicted 211 amino acid protein containing a 29 amino acid signal peptide and two putative N-linked glycosylation sites, whereas the mouse PLP-J cDNA encodes for a 212 amino acid protein containing a 29 amino acid signal peptide with a single N-linked glycosylation site. Rat and mouse PLP-J proteins share approximately 79% and 70% nucleotide and amino acid sequence identity, respectively. A full-length rat PLP-K cDNA and a partial tentative mouse PLP-K cDNA were identified. The rat PLP-K cDNA encodes for a predicted 228 amino acid protein containing a 31 amino acid signal peptide and one putative N-linked glycosylation site; the mouse PLP-M cDNA encodes for a predicted 228 amino acid protein containing a 28 amino acid signal peptide and one putative N-linked glycosylation site. Genes for PLP-J, PLP-K and PLP-M are situated at the Prl family locus on mouse chromosome 13. PLP-J was exclusively expressed in decidual tissue from both the mouse and rat. PLP-K was expressed in trophoblast cells of the chorioallantoic placenta and showed an apparent species difference. In the mouse, virtually all trophoblast lineages expressed PLP-K, whereas in the rat, PLP-K expression was restricted to the labyrinthine trophoblast cells. Mouse PLP-M expression was restricted to the junctional zone of the chorioallantoic placenta. In summary, we have identified three new members of the rodent PRL gene family that are expressed in uterine and placental structures. Future experimentation is needed to determine the specific roles of each of these ligands in the biology of pregnancy.

scholarly journals A Cytosolic STIM2 Preprotein Created by Signal Peptide Inefficiency Activates ORAI1 in a Store-independent Manner

2011 ◽  
Vol 286 (18) ◽  
pp. 16174-16185 ◽  
Author(s):  
Sarah J. L. Graham ◽  
Marie A. Dziadek ◽  
Lorna S. Johnstone
Keyword(s):  
Plasma Membrane ◽  
Gene Transcription ◽  
Signal Peptide ◽  
Independent Manner ◽  
Methionine Residue ◽  
Store Depletion ◽  
Amino Acid Signal Peptide ◽  
Er Targeting ◽  
Amino Acid Signal ◽  
Er Membrane

Calcium (Ca2+) influx through the plasma membrane store-operated Ca2+ channel ORAI1 is controlled by Ca2+ sensors of the stromal interaction molecule (STIM) family. STIM1 responds to endoplasmic reticulum (ER) Ca2+ store depletion by redistributing and activating ORAI1 from regions of the ER juxtaposed to the plasma membrane. Unlike STIM1, STIM2 can regulate ORAI1 in a store-dependent and store-independent manner, but the mechanism by which this is achieved is unknown. Here we find that STIM2 is translated from a highly conserved methionine residue and is directed to the ER by an incredibly long 101-amino acid signal peptide. We find that although the majority of the total STIM2 population resides on the ER membrane, a second population escapes ER targeting to accumulate as a full-length preprotein in the cytosol, signal peptide intact. Unlike STIM2, preSTIM2 localizes to the inner leaflet of the plasma membrane where it interacts with ORAI1 to regulate basal Ca2+ concentration and Ca2+-dependent gene transcription in a store-independent manner. Furthermore, a third protein comprising a fragment of the STIM2 signal peptide is released from the ER membrane into the cytosol where it regulates gene transcription in a Ca2+-independent manner. This study establishes a new model for STIM2-mediated regulation of ORAI1 in which two distinct proteins, STIM2 and preSTIM2, control store-dependent and store-independent modes of ORAI1 activation.

scholarly journals Identification of a novel mutation in the autoimmune regulator (AIRE-1) gene in a French family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

2001 ◽  
pp. 347-351 ◽  
Author(s):  
P Saugier-Veber ◽  
N Drouot ◽  
LM Wolf ◽  
JM Kuhn ◽  
T Frebourg ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Novel Mutation ◽  
Autosomal Recessive Inheritance ◽  
Chronic Mucocutaneous Candidiasis ◽  
Autoimmune Regulator ◽  
Autoimmune Polyendocrinopathy ◽  
Plant Homeodomain ◽  
French Family

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is clinically characterized by the presence of two of the three major clinical symptoms: Addison's disease and/or hypoparathyroidism and/or chronic mucocutaneous candidiasis. Because of its autosomal recessive inheritance, this rare disorder constitutes an interesting model for understanding the molecular background of autoimmunity. Recently, mutations in the autoimmune regulator (AIRE-1) gene have been identified in APECED patients. Here we report, in a large French APECED family, the identification of a novel AIRE-1 missense mutation (Pro326Leu) in association with the Arg257Stop mutation which is detected in more than 80% of mutant Finnish AIRE-1 alleles. This Pro326Leu substitution occurs in the first plant homeodomain (PHD)-type zinc-finger domain of the protein which has been identified in a number of nuclear proteins involved in chromatin-mediated transcriptional regulation, such as ATRX, TIF1, KRIP-1 and Mi-2 autoantigen. This mutation highlights the key role of this amino acid in the structure of the PHD domain and confirms that exon 8 constitutes a mutational hotspot.

Congenital Deficiency of Fibrin-stabilizing Factor (Factor XIII): A Report of Four Cases (Two Families) and Family Members

Blood ◽  
1972 ◽  
Vol 40 (1) ◽  
pp. 11-15 ◽  
Author(s):  
Mohammed A. Aziz ◽  
Azizur Rehman Siddiqui
Keyword(s):  
Factor Xiii ◽  
Autosomal Recessive ◽  
Family Members ◽  
Autosomal Recessive Inheritance ◽  
The Other ◽  
Recessive Inheritance ◽  
Factor Xiii Deficiency ◽  
Congenital Deficiency

Abstract Four patients with congenital deficiency of fibrin-stabilizing factor (factor XIII) from two families have been described. The mother and the sibs in one family and both parents in the other family were found to have varying degrees of factor XIII deficiency. The observations support the hypothesis of autosomal recessive inheritance of factor XIII deficiency.

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