Presentation is loading. Please wait.

Presentation is loading. Please wait.

Mental Retardation and Abnormal Skeletal Development (Dyggve-Melchior-Clausen Dysplasia) Due to Mutations in a Novel, Evolutionarily Conserved Gene  Daniel.

Published byRiitta-Liisa Heikkinen Modified over 5 years ago

Similar presentations

Presentation on theme: "Mental Retardation and Abnormal Skeletal Development (Dyggve-Melchior-Clausen Dysplasia) Due to Mutations in a Novel, Evolutionarily Conserved Gene  Daniel."— Presentation transcript:

1 Mental Retardation and Abnormal Skeletal Development (Dyggve-Melchior-Clausen Dysplasia) Due to Mutations in a Novel, Evolutionarily Conserved Gene  Daniel H. Cohn, Nadia Ehtesham, Deborah Krakow, Sheila Unger, Alan Shanske, Kent Reinker, Berkley R. Powell, David L. Rimoin  The American Journal of Human Genetics  Volume 72, Issue 2, Pages (February 2003) DOI: /346176 Copyright © 2003 The American Society of Human Genetics Terms and Conditions

2 Figure 1 Left panel, Lateral view of the spine, showing platyspondyly and the characteristic double-humped appearance of the vertebral bodies with anterior beaking. Right panel, Antero-posterior view of the hips, showing short, widened ilia with a lacy appearance of the iliac crests. The acetabulae are hypoplastic and irregular. The proximal femoral necks are short, with irregular metaphyses and epiphyses. The American Journal of Human Genetics  , DOI: ( /346176) Copyright © 2003 The American Society of Human Genetics Terms and Conditions

3 Figure 2 Mutations in DMC. a, Chromatograms showing the mutation in family R and (below) a normal sequence. The sequence, with the mutant nucleotide and the corresponding normal nucleotide identified with an arrow, is shown above, and the reading frame is underlined. The nucleotide sequence is numbered from the beginning of the coding sequence. The pedigree, demonstrating segregation of the mutation in the family, is shown to the right. b, Chromatograms showing the mutation in family R02-106, together with a normal sequence. An arrow identifies the mutant nucleotide and the corresponding normal nucleotide, and the reading frame is underlined. A vertical line identifies the exon-intron junction. Segregation of the mutation in the family is shown on the pedigree to the right. c, Chromatograms showing the two mutations identified in family R The reading frame is underlined, and, in each panel, an arrow identifies the normal (above) and mutant (below) sequences. Segregation of the mutations in the family is shown on the pedigree to the right. The American Journal of Human Genetics  , DOI: ( /346176) Copyright © 2003 The American Society of Human Genetics Terms and Conditions

4 Figure 3 Comparison of the protein sequences of FLJ90130 and homologous proteins in other species. ClustalW was used for the alignment. The species from which each sequence is derived is shown on the left (M. musculus [Mm], D. melanogaster [Dm], A. gambiae [Ag], C. elegans [Ce], and A. thaliana [At]), and the amino acid residue numbers are shown on the right. Colors are used to indicate classes of amino acid residues, including hydrophobic and aromatic (green), acidic (blue), basic (dark red), and hydrophilic (green) residues. Symbols below the amino acid sequences indicate identity (*), presence of conserved substitutions (:), or presence of semiconserved substitutions (.). A gray background highlights the residues changed by the two identified missense mutations, E87 and N469. The American Journal of Human Genetics  , DOI: ( /346176) Copyright © 2003 The American Society of Human Genetics Terms and Conditions

5 Figure 3 Comparison of the protein sequences of FLJ90130 and homologous proteins in other species. ClustalW was used for the alignment. The species from which each sequence is derived is shown on the left (M. musculus [Mm], D. melanogaster [Dm], A. gambiae [Ag], C. elegans [Ce], and A. thaliana [At]), and the amino acid residue numbers are shown on the right. Colors are used to indicate classes of amino acid residues, including hydrophobic and aromatic (green), acidic (blue), basic (dark red), and hydrophilic (green) residues. Symbols below the amino acid sequences indicate identity (*), presence of conserved substitutions (:), or presence of semiconserved substitutions (.). A gray background highlights the residues changed by the two identified missense mutations, E87 and N469. The American Journal of Human Genetics  , DOI: ( /346176) Copyright © 2003 The American Society of Human Genetics Terms and Conditions

6 Figure 4 Mutations in SMC. a, Chromatograms showing the two mutations identified in families R and R For the E87K mutation, shown above, the reading frame is underlined, and the arrow identifies the normal (above) and mutant (below) sequences. For the exon-skipping mutation, the smaller arrow identifies the normal (above) and mutant (below) sequences. The intron-exon junction is identified with a vertical line and marked with the larger arrow. Segregation of the mutations in each family is shown on the pedigrees to the right. b, Skipping of exon 8 in cartilage RNA from an affected member of each family. On the left, an image of the agarose gel used to separate the amplified cDNA fragments from cartilage of patient II-5 in family R (“A”) and patient III-2 in family R (“B”), along with a fragment derived from normal fetal cartilage (“C”). Fragment sizes are indicated to the left. The chromatogram on the right shows the sequence across the exon 7/exon 9 boundary, which is identified by a vertical line, in the shorter cDNA fragment from patient II-5 in family R The American Journal of Human Genetics  , DOI: ( /346176) Copyright © 2003 The American Society of Human Genetics Terms and Conditions

7 Figure 5 Structure of the FLJ90130 protein, with the six predicted transmembrane domains shown in yellow. The beginning and ending residues of each transmembrane segment are indicated. Shown below are the predicted consequences of each mutation on the protein sequence/structure in the three DMC and two SMC families studied. Where the mutation results in a frameshift, the portion of the protein beyond the frameshift is indicated in red. The locations of missense mutations are identified with a dot and the specific protein-sequence change. The American Journal of Human Genetics  , DOI: ( /346176) Copyright © 2003 The American Society of Human Genetics Terms and Conditions

Download ppt "Mental Retardation and Abnormal Skeletal Development (Dyggve-Melchior-Clausen Dysplasia) Due to Mutations in a Novel, Evolutionarily Conserved Gene  Daniel."

Similar presentations

Protein-Truncation Mutations in the RP2 Gene in a North American Cohort of Families with X-Linked Retinitis Pigmentosa  Alan J. Mears, Linn Gieser, Denise.

Protein-Truncation Mutations in the RP2 Gene in a North American Cohort of Families with X-Linked Retinitis Pigmentosa  Alan J. Mears, Linn Gieser, Denise.
Novel PMS2 Pseudogenes Can Conceal Recessive Mutations Causing a Distinctive Childhood Cancer Syndrome  Michel De Vos, Bruce E. Hayward, Susan Picton,

Novel PMS2 Pseudogenes Can Conceal Recessive Mutations Causing a Distinctive Childhood Cancer Syndrome  Michel De Vos, Bruce E. Hayward, Susan Picton,
Volume 7, Issue 10, Pages (October 2010)

Volume 7, Issue 10, Pages (October 2010)
A Novel Mutation and Large Size Polymorphism Affecting the V2 Domain of Keratin 1 in an African-American Family with Severe, Diffuse Palmoplantar Keratoderma.

A Novel Mutation and Large Size Polymorphism Affecting the V2 Domain of Keratin 1 in an African-American Family with Severe, Diffuse Palmoplantar Keratoderma.
A Dual Phenotype of Periventricular Nodular Heterotopia and Frontometaphyseal Dysplasia in One Patient Caused by a Single FLNA Mutation Leading to Two.

A Dual Phenotype of Periventricular Nodular Heterotopia and Frontometaphyseal Dysplasia in One Patient Caused by a Single FLNA Mutation Leading to Two.
Identification of a Frameshift Mutation in Osterix in a Patient with Recessive Osteogenesis Imperfecta  Pablo Lapunzina, Mona Aglan, Samia Temtamy, José.

Identification of a Frameshift Mutation in Osterix in a Patient with Recessive Osteogenesis Imperfecta  Pablo Lapunzina, Mona Aglan, Samia Temtamy, José.
P. M. Kelley, D. J. Harris, B. C. Comer, J. W. Askew, T. Fowler, S. D

P. M. Kelley, D. J. Harris, B. C. Comer, J. W. Askew, T. Fowler, S. D
Familial Deafness, Congenital Heart Defects, and Posterior Embryotoxon Caused by Cysteine Substitution in the First Epidermal-Growth-Factor–Like Domain.

Familial Deafness, Congenital Heart Defects, and Posterior Embryotoxon Caused by Cysteine Substitution in the First Epidermal-Growth-Factor–Like Domain.
Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A

Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A
Mutations in the Liver Glycogen Phosphorylase Gene (PYGL) Underlying Glycogenosis Type VI (Hers Disease)  Barbara Burwinkel, Henk D. Bakker, Eliezer Herschkovitz,

Mutations in the Liver Glycogen Phosphorylase Gene (PYGL) Underlying Glycogenosis Type VI (Hers Disease)  Barbara Burwinkel, Henk D. Bakker, Eliezer Herschkovitz,
The Molecular Basis of Malonyl-CoA Decarboxylase Deficiency

The Molecular Basis of Malonyl-CoA Decarboxylase Deficiency
Michael Field, Patrick S

Michael Field, Patrick S
Mutations in ZDHHC9, Which Encodes a Palmitoyltransferase of NRAS and HRAS, Cause X-Linked Mental Retardation Associated with a Marfanoid Habitus  F.

Mutations in ZDHHC9, Which Encodes a Palmitoyltransferase of NRAS and HRAS, Cause X-Linked Mental Retardation Associated with a Marfanoid Habitus  F.
Factor H Mutations in Hemolytic Uremic Syndrome Cluster in Exons 18–20, a Domain Important for Host Cell Recognition  Anna Richards, Mark R. Buddles,

Factor H Mutations in Hemolytic Uremic Syndrome Cluster in Exons 18–20, a Domain Important for Host Cell Recognition  Anna Richards, Mark R. Buddles,
Mutations in DDR2 Gene Cause SMED with Short Limbs and Abnormal Calcifications  Ruth Bargal, Valerie Cormier-Daire, Ziva Ben-Neriah, Martine Le Merrer,

Mutations in DDR2 Gene Cause SMED with Short Limbs and Abnormal Calcifications  Ruth Bargal, Valerie Cormier-Daire, Ziva Ben-Neriah, Martine Le Merrer,
Volume 54, Issue 3, Pages (September 1998)

Volume 54, Issue 3, Pages (September 1998)
Sequence Analysis and Homology Modeling Suggest That Primary Congenital Glaucoma on 2p21 Results from Mutations Disrupting Either the Hinge Region or.

Sequence Analysis and Homology Modeling Suggest That Primary Congenital Glaucoma on 2p21 Results from Mutations Disrupting Either the Hinge Region or.
Gail Billingsley, Sathiyavedu T. Santhiya, Andrew D

Gail Billingsley, Sathiyavedu T. Santhiya, Andrew D
Mutations in a Novel Gene with Transmembrane Domains Underlie Usher Syndrome Type 3  Tarja Joensuu, Riikka Hämäläinen, Bo Yuan, Cheryl Johnson, Saara.

Mutations in a Novel Gene with Transmembrane Domains Underlie Usher Syndrome Type 3  Tarja Joensuu, Riikka Hämäläinen, Bo Yuan, Cheryl Johnson, Saara.
(A) Six missense mutations in six essential genes that are not in annotated functional domains. (A) Six missense mutations in six essential genes that.

(A) Six missense mutations in six essential genes that are not in annotated functional domains. (A) Six missense mutations in six essential genes that.

Similar presentations

Ads by Google