Search Our Scientific Publications & Authors

Publications
find publications by category +
Translate page:

A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family.

Authors:
Muzammil A Khan Verena M Rupp Meritxell Orpinell Muhammad S Hussain Janine Altmüller Michel O Steinmetz Christian Enzinger Holger Thiele Wolfgang Höhne Gudrun Nürnberg Shahid M Baig Muhammad Ansar Peter Nürnberg John B Vincent Michael R Speicher Pierre Gönczy Christian Windpassinger

Hum Mol Genet 2014 Nov 20;23(22):5940-9. Epub 2014 Jun 20.

Institute of Human Genetics and

Asymmetric cell division is essential for normal human brain development. Mutations in several genes encoding centrosomal proteins that participate in accurate cell division have been reported to cause autosomal recessive primary microcephaly (MCPH). By homozygosity mapping including three affected individuals from a consanguineous MCPH family from Pakistan, we delineated a critical region of 18.53 Mb on Chromosome 1p21.3-1p13.1. This region contains the gene encoding HsSAS-6, a centrosomal protein primordial for seeding the formation of new centrioles during the cell cycle. Both next-generation and Sanger sequencing revealed a homozygous c.185T>C missense mutation in the HsSAS-6 gene, resulting in a p.Ile62Thr substitution within a highly conserved region of the PISA domain of HsSAS-6. This variant is neither present in any single-nucleotide polymorphism or exome sequencing databases nor in a Pakistani control cohort. Experiments in tissue culture cells revealed that the Ile62Thr mutant of HsSAS-6 is substantially less efficient than the wild-type protein in sustaining centriole formation. Together, our findings demonstrate a dramatic impact of the mutation p.Ile62Thr on HsSAS-6 function and add this component to the list of genes mutated in primary microcephaly.

Download full-text PDF

 Source
http://dx.doi.org/10.1093/hmg/ddu318DOI Listing
November 2014

Publication Analysis

Top Keywords

primary microcephaly
12
pisa domain
8
cell division
8
autosomal recessive
8
domain hssas-6
8
recessive primary
8
missense mutation
8
hssas-6
6
chromosome 1p213-1p131
4
databases pakistani
4
1p213-1p131 region
4
encoding hssas-6
4
gene encoding
4
region gene
4
centrosomal protein
4
seeding formation
4
sustaining centriole
4
primordial seeding
4
protein primordial
4
1853 chromosome
4

Keyword Occurance

Similar Publications

A Possible Association Between Zika Virus Infection and CDK5RAP2 Mutation.

Authors:
Estephania Candelo Ana Maria Sanz Diana Ramirez-Montaño Lorena Diaz-Ordoñez Ana Maria Granados Fernando Rosso Julian Nevado Pablo Lapunzina Harry Pachajoa

Front Genet 2021 19;12:530028. Epub 2021 Mar 19.

Center for Research on Congenital Anomalies and Rare Diseases (CIACER), Department of Basic Medical Sciences, Universidad Icesi, Cali, Colombia.

Introduction: Flaviviridae family belongs to the Spondweni serocomplex, which is mainly transmitted by vectors from the genus. Zika virus (ZIKV) is part of this genus. It was initially reported in Brazil in December 2014 as an unknown acute generalized exanthematous disease and was subsequently identified as ZIKV infection. Read More

View Article and Full-Text PDF
March 2021
Similar Publications

CENPE Inhibition Leads to Mitotic Catastrophe and DNA Damage in Medulloblastoma Cells.

Authors:
Giorgia Iegiani Marta Gai Ferdinando Di Cunto Gianmarco Pallavicini

Cancers (Basel) 2021 Mar 1;13(5). Epub 2021 Mar 1.

Neuroscience Institute Cavalieri Ottolenghi, 10043 Turin, Italy.

Medulloblastoma (MB) is the most frequent brain tumor in children. The standard treatment consists in surgery, followed by radiotherapy and chemotherapy. These therapies are only partially effective since many patients still die and those who survive suffer from neurological and endocrine disorders. Read More

View Article and Full-Text PDF
March 2021
Similar Publications

Novel variant in BRAT1 with the lethal neonatal rigidity and multifocal seizure syndrome.

Authors:
Weixi Li Shuiyan Wu Huizhong Xu Xiaoying Zhao Yizhi Pan Hongbiao Huang Haitao Lv Xueping Zhu Ying Liu

Pediatr Res 2021 Mar 31. Epub 2021 Mar 31.

Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, People's Republic of China.

Background: Lethal neonatal rigidity and multifocal seizure syndrome (RMFSL) is caused by variants in BRAT1 (BRCA1-associated protein required for ATM activation-1). However, the molecular mechanism of RMFSL is still unclear.

Methods: An RMFSL infant was recruited and the peripheral blood samples from his trio-family were collected. Read More

View Article and Full-Text PDF
March 2021
Similar Publications

Primary Dwarfism, Microcephaly, and Chorioretinopathy due to a PLK4 Mutation in Two Siblings.

Authors:
Álvaro Martín-Rivada Jesús Pozo-Román María Güemes Nelmar Valentina Ortiz-Cabrera Luis A Pérez-Jurado Jesús Argente

Horm Res Paediatr 2021 Mar 23:1-6. Epub 2021 Mar 23.

Departments of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Research Institute "La Princesa,", Madrid, Spain,

Introduction: Primary autosomal recessive microcephalies (MCPHs) are characterized by primary dwarfism with MCPH and may present delayed psychomotor development and visual impairment. Biallelic loss of function variants in the PLK4 gene, which encodes the polo-like kinase 4 protein involved in centriole biogenesis, has been recently identified in several patients with MCPH and various ethnic backgrounds.

Case Presentation: Here, we describe 2 siblings of different sex from Equatorial Guinea harboring a homozygous frameshift mutation in PLK4 (c. Read More

View Article and Full-Text PDF
March 2021
Similar Publications

Inhibition of innate immune response ameliorates Zika virus-induced neurogenesis deficit in human neural stem cells.

Authors:
Pei Xu Junling Gao Chao Shan Tiffany J Dunn Xuping Xie Hongjie Xia Jing Zou Beatriz H Thames Amulya Sajja Yongjia Yu Alexander N Freiberg Nikos Vasilakis Pei-Yong Shi Scott C Weaver Ping Wu

PLoS Negl Trop Dis 2021 Mar 3;15(3):e0009183. Epub 2021 Mar 3.

Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, Texas, United States of America.

Global Zika virus (ZIKV) outbreaks and their strong link to microcephaly have raised major public health concerns. ZIKV has been reported to affect the innate immune responses in neural stem/progenitor cells (NS/PCs). However, it is unclear how these immune factors affect neurogenesis. Read More

View Article and Full-Text PDF
March 2021
Similar Publications