Presentation is loading. Please wait.

Presentation is loading. Please wait.

Exome Sequencing Extends the Phenotypic Spectrum for ABHD12 Mutations

Published byAntoon Visser Modified over 6 years ago

Similar presentations

Presentation on theme: "Exome Sequencing Extends the Phenotypic Spectrum for ABHD12 Mutations"— Presentation transcript:

1 Exome Sequencing Extends the Phenotypic Spectrum for ABHD12 Mutations
Koji M. Nishiguchi, PhD, MD, Almudena Avila-Fernandez, PhD, Ramon A.C. van Huet, MD, Marta Corton, PhD, Raquel Pérez-Carro, MSc, Esther Martín-Garrido, MSc, María Isabel López-Molina, MD, Fiona Blanco-Kelly, MD, PhD, Lies H. Hoefsloot, PhD, Wendy A. van Zelst-Stams, MD, PhD, Pedro J. García-Ruiz, MD, Javier del Val, MD, Silvio Alessandro Di Gioia, PhD, B. Jeroen Klevering, MD, PhD, Bart P.C. van de Warrenburg, MD, PhD, Carlos Vazquez, MD, Frans P.M. Cremers, PhD, Blanca García-Sandoval, MD, PhD, Carel B. Hoyng, MD, PhD, Rob W.J. Collin, PhD, Carlo Rivolta, PhD, Carmen Ayuso, MD, PhD  Ophthalmology  Volume 121, Issue 8, Pages (August 2014) DOI: /j.ophtha Copyright © 2014 American Academy of Ophthalmology Terms and Conditions

2 Figure 1 A, Pedigrees of the 3 studied families with ABHD12 mutations. The index case is indicated with an arrow. Sanger sequencing confirmed the mutations identified by whole exome sequencing (WES) and revealed their complete cosegregation with the disease. The chromatograms of a mutant and a control individual are depicted for each variant (arrows). B, Cross-species comparison of 3 regions of ABHD12 indicates that the 3 identified missense mutations affect highly conserved residues. C, Three-dimensional structural model of ABHD12. The Ile amino acid residue at position 202 (purple) may lead to distortion of the active site (yellow) of the other monomer. For variant p.His372Gln, the Gln amino acid residue at position 372 (red) does not seem to impair the predicted structure of the protein. The His residue is shown in orange. For variant p.Arg186Pro, the change, Arg (green) to Pro (red), seems to disturb the predicted structure of the protein. The hydrogen bonds and hydrophobic interactions are shown in yellow. D, Intron–exon structure of ABHD12 and location of all mutations identified so far. Mutations previously associated with polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and early-onset cataract (PHARC) syndrome or PHARC-like syndrome are shown in black. Red exons indicate the α-β hydrolyze domain of the protein. The mutations identified in this study and associated with PHARC syndrome or nonsyndromic retinitis pigmentosa are shown in red. Ophthalmology  , DOI: ( /j.ophtha ) Copyright © 2014 American Academy of Ophthalmology Terms and Conditions

3 Figure 2 Phenotype of patients from the RP-1292 and W families with mutations in the ABHD12 gene. A, Spectrum of fundus findings in different individuals. Funduscopy of 3 patients of the RP-1292 family (II:4, II:5, and II:7) shows pale optic discs, attenuation of retinal vessels, and bone spicule pigmentation. Funduscopy of patient II:1 of the W family shows pallor of the optic disc, attenuation of the arterioles, and parafoveal atrophy with bull's-eye appearance B, Pure-tone air conduction audiograms of the patients. The grey areas are the hearing ranges for normal individual at 70 to 79 years of age (women), 70 to 79 years of age (men), and 60 to 69 years of age (men), respectively, as reported by Cruickshanks et al.32 Family RP-1292: for patients II:4 (female) and II:7 (male), the audiogram shows age-related hearing loss. Audiogram of the patient II:5 (male) shows hearing loss of the right ear. Family W : audiogram of the patient II:1 shows sensorineural hearing loss of both eyes. C, Magnetic resonance imaging (MRI) scans. Family RP-1292: for patient II:4, MRI scan shows minimal cerebral atrophy (white arrow), whereas in patient II:5, some injuries in the left cerebellum hemisphere consistent with the consequence of an ischemic event (white arrow) are present. Patient II:7 has a minimal abnormality probably resulting from an ischemic injury (white arrow). Family W : for patient II:1, no structural abnormalities of the cerebellum are observed. Ophthalmology  , DOI: ( /j.ophtha ) Copyright © 2014 American Academy of Ophthalmology Terms and Conditions

Download ppt "Exome Sequencing Extends the Phenotypic Spectrum for ABHD12 Mutations"

Similar presentations

Date of download: 5/30/2016 Copyright © 2016 American Medical Association. All rights reserved. From: An Unusual Retinal Phenotype Associated With a Novel.

Date of download: 5/30/2016 Copyright © 2016 American Medical Association. All rights reserved. From: An Unusual Retinal Phenotype Associated With a Novel.
Microcystic Macular Edema

Microcystic Macular Edema
Volume 123, Issue 5, Pages (May 2016)

Volume 123, Issue 5, Pages (May 2016)
Germline Missense Mutations Affecting KRAS Isoform B Are Associated with a Severe Noonan Syndrome Phenotype  Claudio Carta, Francesca Pantaleoni, Gianfranco.

Germline Missense Mutations Affecting KRAS Isoform B Are Associated with a Severe Noonan Syndrome Phenotype  Claudio Carta, Francesca Pantaleoni, Gianfranco.
Mesial temporal lobe epilepsy associated with KCNT1 mutation

Mesial temporal lobe epilepsy associated with KCNT1 mutation
A Mutation in HOXA2 Is Responsible for Autosomal-Recessive Microtia in an Iranian Family  Fatemeh Alasti, Abdorrahim Sadeghi, Mohammad Hossein Sanati,

A Mutation in HOXA2 Is Responsible for Autosomal-Recessive Microtia in an Iranian Family  Fatemeh Alasti, Abdorrahim Sadeghi, Mohammad Hossein Sanati,
Figure 1 Phenotype and genotype of an undiagnosed family with autosomal recessive spastic ataxia Phenotype and genotype of an undiagnosed family with autosomal.

Figure 1 Phenotype and genotype of an undiagnosed family with autosomal recessive spastic ataxia Phenotype and genotype of an undiagnosed family with autosomal.
Mutations in IMPG1 Cause Vitelliform Macular Dystrophies

Mutations in IMPG1 Cause Vitelliform Macular Dystrophies
Homozygosity Mapping Reveals Mutations of GRXCR1 as a Cause of Autosomal- Recessive Nonsyndromic Hearing Impairment  Margit Schraders, Kwanghyuk Lee, Jaap.

Homozygosity Mapping Reveals Mutations of GRXCR1 as a Cause of Autosomal- Recessive Nonsyndromic Hearing Impairment  Margit Schraders, Kwanghyuk Lee, Jaap.
MYO6, the Human Homologue of the Gene Responsible for Deafness in Snell’s Waltzer Mice, Is Mutated in Autosomal Dominant Nonsyndromic Hearing Loss  Salvatore.

MYO6, the Human Homologue of the Gene Responsible for Deafness in Snell’s Waltzer Mice, Is Mutated in Autosomal Dominant Nonsyndromic Hearing Loss  Salvatore.
Grouping of Multiple-Lentigines/LEOPARD and Noonan Syndromes on the PTPN11 Gene  Maria Cristina Digilio, Emanuela Conti, Anna Sarkozy, Rita Mingarelli,

Grouping of Multiple-Lentigines/LEOPARD and Noonan Syndromes on the PTPN11 Gene  Maria Cristina Digilio, Emanuela Conti, Anna Sarkozy, Rita Mingarelli,
Pedigrees of the families of patients 1 and 2 show that the clinical phenotype co-segregates with compound heterozygous CLDN10 variants. Pedigrees of the.

Pedigrees of the families of patients 1 and 2 show that the clinical phenotype co-segregates with compound heterozygous CLDN10 variants. Pedigrees of the.
Figure Cerebral MRI and molecular and enzymatic analysis

Figure Cerebral MRI and molecular and enzymatic analysis
Novel mutations and polymorphisms in the CFTR gene associated with three subtypes of congenital absence of vas deferens  Xiaojian Yang, M.D., Qipeng Sun,

Novel mutations and polymorphisms in the CFTR gene associated with three subtypes of congenital absence of vas deferens  Xiaojian Yang, M.D., Qipeng Sun,
A Missense Mutation in PRPF6 Causes Impairment of pre-mRNA Splicing and Autosomal-Dominant Retinitis Pigmentosa  Goranka Tanackovic, Adriana Ransijn,

A Missense Mutation in PRPF6 Causes Impairment of pre-mRNA Splicing and Autosomal-Dominant Retinitis Pigmentosa  Goranka Tanackovic, Adriana Ransijn,
A novel mutation c.118delA in exon 1 of the androgen receptor gene resulting in complete androgen insensitivity syndrome within a large family  Karel.

A novel mutation c.118delA in exon 1 of the androgen receptor gene resulting in complete androgen insensitivity syndrome within a large family  Karel.
A Patient With Hereditary ATTR and a Novel AGel p

A Patient With Hereditary ATTR and a Novel AGel p
The 2588G→C Mutation in the ABCR Gene Is a Mild Frequent Founder Mutation in the Western European Population and Allows the Classification of ABCR Mutations.

The 2588G→C Mutation in the ABCR Gene Is a Mild Frequent Founder Mutation in the Western European Population and Allows the Classification of ABCR Mutations.
Structure Prediction: How good are we?

Structure Prediction: How good are we?
A Nonsense Mutation in PDE6H Causes Autosomal-Recessive Incomplete Achromatopsia  Susanne Kohl, Frauke Coppieters, Françoise Meire, Simone Schaich, Susanne.

A Nonsense Mutation in PDE6H Causes Autosomal-Recessive Incomplete Achromatopsia  Susanne Kohl, Frauke Coppieters, Françoise Meire, Simone Schaich, Susanne.

Similar presentations

Ads by Google