Related Experiment Video

Updated: May 23, 2026

Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease
12:47

Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease

Published on: February 3, 2012

NEK1 and DYNC2H1 are both involved in short rib polydactyly Majewski type but not in Beemer Langer cases

Joyce El Hokayem1, Céline Huber, Adeline Couvé

  • 1Department of Genetics, INSERM U781, Hôpital Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris 75015, France.

Journal of Medical Genetics
|April 14, 2012
PubMed
Abstract

Insights

This study identifies NEK1 and DYNC2H1 mutations in short rib polydactyly syndrome type II (SRP type II), expanding the known genetic causes. Further research is needed as some SRP type II and IV cases remain genetically unexplained.

Area of Science:

  • Genetics
  • Developmental Biology
  • Medical Genetics

Background:

  • Short rib polydactyly syndromes (SRP) are lethal skeletal dysplasias with autosomal recessive inheritance.
  • SRP type II (Majewski) and SRP type IV (Beemer-Langer) are distinct but radiographically similar subtypes.
  • NEK1 mutations were previously linked to SRP type II, and digenic inheritance involving NEK1 and DYNC2H1 was suggested.

Purpose of the Study:

  • To investigate the roles of NEK1 and DYNC2H1 in SRP type II and SRP type IV.
  • To identify the genetic basis for SRP in affected individuals.

Main Methods:

  • Genetic screening of NEK1 and DYNC2H1 in 13 SRP type II and 7 SRP type IV patients.
  • Analysis of mutation presence and inheritance patterns.

Main Results:

  • Homozygous NEK1 mutations found in 5/13 SRP type II cases.
  • Compound heterozygous DYNC2H1 mutations identified in 4/12 SRP type II cases.
  • NEK1 and DYNC2H1 were excluded in 3 SRP type II and all SRP type IV cases, with holoprosencephaly/polymicrogyria noted in mutation-negative SRP type II patients.

Conclusions:

  • NEK1 is confirmed as a causative gene for SRP type II.
  • DYNC2H1 mutations are identified in SRP type II, broadening its phenotypic spectrum.
  • Genetic heterogeneity for SRP type II and IV is supported by unexplained cases.

More Related Videos

In Situ Detection of Ribonucleoprotein Complex Assembly in the C. elegans Germline using Proximity Ligation Assay08:56

In Situ Detection of Ribonucleoprotein Complex Assembly in the C. elegans Germline using Proximity Ligation Assay

Published on: May 5, 2020

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations08:22

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

Related Concept Videos

Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
Lethal Alleles02:41

Lethal Alleles

Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Cytoskeletal Linker Proteins - Plakins01:09

Cytoskeletal Linker Proteins - Plakins

Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
Nondisjunction01:29

Nondisjunction

During meiosis, chromosomes occasionally separate improperly. This occurs due to failure of homologous chromosome separation during meiosis I or failed sister chromatid separation during meiosis II. In some species, notably plants, nondisjunction can result in an organism with an entire additional set of chromosomes, which is called polyploidy. In humans, nondisjunction can occur during male or female gametogenesis and the resulting gametes possess one too many or one too few chromosomes.