NDLI: Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes

Content Provider	Springer Nature Link
Author	Russo, S. Marchi, M. Cogliati, F. Bonati, M. T. Pintaudi, M. Veneselli, E. Saletti, V. Balestrini, M. Ben Zeev, B. Larizza, L.
Copyright Year	2009
Abstract	It has been found that CDKL5 gene mutations are responsible for early-onset epilepsy and drug resistance. We screened a population of 92 patients with classic/atypical Rett syndrome, 17 Angelman/Angelman-like patients and six idiopathic autistic patients for CDKL5 mutations and exon deletions and identified seven novel mutations: six in the Rett subset and one in an Angelman patient. This last, an insertion in exon 11, c.903_904 dupGA, p.Leu302Aspfx49X, is associated with a relatively mild clinical presentation as the patient is the only one capable of sitting and walking alone. Of the six mutations, two are de novo missense changes affecting highly conserved aminoacid residues, c.215 T > C p.Ile72Thr and c.380A > G p.His127Arg (present in a mosaic condition) found in two girls with the most severe clinical presentation, while the remaining are the splicing c.145 + 2 T > C and c.2376 + 5G > A, the c.1648C > T p.Arg550X and the MPLA-identified c.162_99del261 mutation. RNA characterisation of four mutations revealed the aberrant transcript of the missense allele (case 2) and not the stop mutation (case 3), but also allowed the splicing mutation (case 1) and the c.-162_99del261 (case 4) to be categorised as truncating. The obtained data reinforce the view that a more severe phenotype is due more to an altered protein than haploinsufficiency. Furthermore, the mutational repertoire of the CDKL5 gene is shown to be expanded by testing patients with phenotypical overlap to Rett syndrome and applying multiplex ligation-dependent probe amplification.
Starting Page	241
Ending Page	250
Page Count	10
File Format	PDF
ISSN	13646745
Journal	Neurogenetics
Volume Number	10
Issue Number	3
e-ISSN	13646753
Language	English
Publisher	Springer-Verlag
Publisher Date	2009-02-25
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Mutation screening RNA analysis Genotype–phenotype correlation Neurosciences Molecular Medicine Human Genetics
Content Type	Text
Resource Type	Article
Subject	Genetics Cellular and Molecular Neuroscience Genetics (clinical)

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Clinical features and genotype-phenotype correlation analysis in patients with ATL1 mutations: A literature reanalysis

TRPV4 mutations in children with congenital distal spinal muscular atrophy

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

L239F founder mutation in GDAP1 is associated with a mild Charcot–Marie–Tooth type 4C4 (CMT4C4) phenotype

New mutations in the ATM gene and clinical data of 25 AT patients

Erratum to: Expansion of the spectrum of TUBB4A-related disorders: A new phenotype associated with a novel mutation in the TUBB4A gene

Identification of a novel CDKL5 exon and pathogenic mutations in patients with severe mental retardation, early-onset seizures and Rett-like features

Identification of two novel mutations and of a novel critical region in the KRIT1 gene

Familial cases presenting very early onset autosomal dominant Alzheimer’s disease with I143T in presenilin-1 gene: implication for genotype–phenotype correlation

Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes

Similar Documents

Clinical features and genotype-phenotype correlation analysis in patients with ATL1 mutations: A literature reanalysis

TRPV4 mutations in children with congenital distal spinal muscular atrophy

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

L239F founder mutation in GDAP1 is associated with a mild Charcot–Marie–Tooth type 4C4 (CMT4C4) phenotype

New mutations in the ATM gene and clinical data of 25 AT patients

Erratum to: Expansion of the spectrum of TUBB4A-related disorders: A new phenotype associated with a novel mutation in the TUBB4A gene

Identification of a novel CDKL5 exon and pathogenic mutations in patients with severe mental retardation, early-onset seizures and Rett-like features

Identification of two novel mutations and of a novel critical region in the KRIT1 gene

Familial cases presenting very early onset autosomal dominant Alzheimer’s disease with I143T in presenilin-1 gene: implication for genotype–phenotype correlation

Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes