scholarly journals Autosomal Dominant Stapes Ankylosis with Broad Thumbs and Toes, Hyperopia, and Skeletal Anomalies Is Caused by Heterozygous Nonsense and Frameshift Mutations in NOG, the Gene Encoding Noggin*

2002 ◽  
Vol 71 (3) ◽  
pp. 618-624 ◽  
Author(s):  
David J. Brown ◽  
Theresa B. Kim ◽  
Elizabeth M. Petty ◽  
Catherine A. Downs ◽  
Donna M. Martin ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Gene Encoding ◽  
Frameshift Mutations ◽  
Skeletal Anomalies ◽  
Broad Thumbs

Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2317-2322 ◽  
Author(s):  
David C. Dale ◽  
Richard E. Person ◽  
Audrey Anna Bolyard ◽  
Andrew G. Aprikyan ◽  
Cindy Bos ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Rna Splicing ◽  
Bacterial Infections ◽  
Autosomal Dominant ◽  
Mononuclear Cells ◽  
Mutational Analysis ◽  
Congenital Neutropenia ◽  
Gene Encoding ◽  
Cyclic Neutropenia ◽  
Shwachman Diamond Syndrome

Abstract Congenital neutropenia and cyclic neutropenia are disorders of neutrophil production predisposing patients to recurrent bacterial infections. Recently the locus for autosomal dominant cyclic neutropenia was mapped to chromosome 19p13.3, and this disease is now attributable to mutations of the gene encoding neutrophil elastase (the ELA2 gene). The authors hypothesized that congenital neutropenia is also due to mutations of neutrophil elastase. Patients with congenital neutropenia, cyclic neutropenia, or Shwachman-Diamond syndrome were referred to the Severe Chronic Neutropenia International Registry. Referring physicians provided hematologic and clinical data. Mutational analysis was performed by sequencing polymerase chain reaction (PCR)-amplified genomic DNA for each of the 5 exons of the neutrophil ELA2 gene and 20 bases of the flanking regions. RNA from bone marrow mononuclear cells was used to determine if the affected patients expressed both the normal and the abnormal transcript. Twenty-two of 25 patients with congenital neutropenia had 18 different heterozygous mutations. Four of 4 patients with cyclic neutropenia and 0 of 3 patients with Shwachman-Diamond syndrome had mutations. For 5 patients with congenital neutropenia having mutations predicted to alter RNA splicing or transcript structure, reverse transcriptase-PCR showed expression of both normal and abnormal transcripts. In cyclic neutropenia, the mutations appeared to cluster near the active site of the molecule, whereas the opposite face was predominantly affected by the mutations found in congenital neutropenia. This study indicates that mutations of the gene encoding neutrophil elastase are probably the most common cause for severe congenital neutropenia as well as the cause for sporadic and autosomal dominant cyclic neutropenia.

GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome

1997 ◽  
Vol 15 (3) ◽  
pp. 266-268 ◽  
Author(s):  
Seongman Kang ◽  
John M. Graham ◽  
Ann Haskins Olney ◽  
Leslie G. Biesecker
Keyword(s):  
Autosomal Dominant ◽  
Frameshift Mutations

Oral and Dental Manifestations in Rubinstein-Taybi Syndrome: Report of a Rare Case

2012 ◽  
Vol os19 (1) ◽  
pp. 35-38 ◽  
Author(s):  
Madiraju Gunashekhar ◽  
Mohammad Shahul Hameed ◽  
Syed Kamran Bokhari
Keyword(s):  
Rare Case ◽  
Autosomal Dominant ◽  
Postnatal Growth ◽  
Dominant Inheritance ◽  
Supernumerary Tooth ◽  
Growth Deficiency ◽  
Craniofacial Dysmorphism ◽  
Rare Congenital Disorder ◽  
Broad Thumbs ◽  
Syndrome Report

Rubinstein-Taybi syndrome, or broad thumb-hallux syndrome, is a well-defined rare congenital disorder characterised by postnatal growth deficiency, craniofacial dysmorphism, broad thumbs and great toes, and mental retardation (intellectual disability). Occurrence may be either sporadic or through autosomal dominant inheritance. Reports of Rubinstein-Taybi syndrome are scarce in the literature. This case report describes the oral and dentofacial findings of Rubinstein-Taybi syndrome affecting a 13-year-old Indian female, including the uncommon presence of talon cusps and an unerupted supernumerary tooth.

Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2645-2650 ◽  
Author(s):  
Phil J. Ancliff ◽  
Rosemary E. Gale ◽  
Ri Liesner ◽  
Ian M. Hann ◽  
David C. Linch
Keyword(s):  
Neutrophil Elastase ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Autosomal Recessive Disorder ◽  
Severe Neutropenia ◽  
Base Substitution ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Gene Encoding ◽  
Familial Form

Abstract Severe congenital neutropenia (SCN) was originally described as an autosomal recessive disorder. Subsequently, autosomal dominant and sporadic forms of the disease have been recognized. All forms are manifest by persistent severe neutropenia and recurrent bacterial infection. In contrast, cyclical hematopoiesis is characterized by periodic neutropenia inter-spaced with (near) normal neutrophil counts. Recently, linkage analysis on 13 affected pedigrees identified chromosome 19p13.3 as the likely position for mutations in cyclical hematopoiesis. Heterozygous mutations in the ELA2 gene encoding neutrophil elastase were detected in all families studied. Further work also demonstrated mutations in ELA2 in sporadic and autosomal dominant SCN. However, all mutations described to date are heterozygous and thus appear to act in a dominant fashion, which is inconsistent with an autosomal recessive disease. Therefore, the current study investigated whether mutations in ELA2could account for the disease phenotype in classical autosomal recessive SCN and in the sporadic and autosomal dominant types. All 5 exons of ELA2 and their flanking introns were studied in 18 patients (3 autosomal recessive, 5 autosomal dominant [from 3 kindreds], and 10 sporadic) using direct automated sequencing. No mutations were found in the autosomal recessive families. A point mutation was identified in 1 of 3 autosomal dominant families, and a base substitution was identified in 8 of 10 patients with the sporadic form, though 1 was subsequently shown to be a low-frequency polymorphism. These results suggest that mutations in ELA2are not responsible for classical autosomal recessive Kostmann syndrome but provide further evidence for the role of ELA2 in SCN.

Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy

10.1038/6799 ◽  
1999 ◽  
Vol 21 (3) ◽  
pp. 285-288 ◽  
Author(s):  
Gisèle Bonne ◽  
Marina Raffaele Di Barletta ◽  
Shaida Varnous ◽  
Henri-Marc Bécane ◽  
El-Hadi Hammouda ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Autosomal Dominant ◽  
Lamin A ◽  
Gene Encoding
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