Encephalopathy and bilateral cataract in a boy with an interstitial deletion of Xp22 comprising the CDKL5 and NHS genes

We describe a male patient with a deletion at Xp22, detected by high resolution X‐array CGH. The clinical phenotype present in this infant boy, consists of severe encephalopathy, congenital cataracts and tetralogy of Fallot and can be attributed to the deletion of the genes within the interval. Among these deleted genes are the gene for Nance‐Horan syndrome and the cyclin‐dependent kinase‐like 5 gene (CDKL5), responsible for the early seizure variant of Rett syndrome. This is the first description of a male patient with a deletion of these genes, showing the involvement of CDKL5 in severe epileptic encephalopathy in males. Moreover it illustrates the added value of high resolution array‐CGH in molecular diagnosis of mental retardation‐multiple congenital anomaly cases. © 2007 Wiley‐Liss, Inc.

[1]  R. Zannolli,et al.  Myoclonic encephalopathy in the CDKL5 gene mutation , 2006, Clinical Neurophysiology.

[2]  J. Gécz,et al.  Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. , 2005, American journal of human genetics.

[3]  N. Landsberger,et al.  CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. , 2005, Human molecular genetics.

[4]  J. Gécz,et al.  Early onset seizures and Rett-like features associated with mutations in CDKL5 , 2005, European Journal of Human Genetics.

[5]  P. Marynen,et al.  Deletion of VCX-A due to NAHR plays a major role in the occurrence of mental retardation in patients with X-linked ichthyosis. , 2005, Human molecular genetics.

[6]  P. Marynen,et al.  X chromosome array-CGH for the identification of novel X-linked mental retardation genes. , 2005, European journal of medical genetics.

[7]  A. Renieri,et al.  CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms , 2005, Journal of Medical Genetics.

[8]  P. Ingham,et al.  Retinoic Acid Signaling Restricts the Cardiac Progenitor Pool , 2005, Science.

[9]  J. Gécz,et al.  Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation. , 2004, American journal of human genetics.

[10]  J. Gécz,et al.  Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are associated with severe neurodevelopmental retardation. , 2004, American journal of human genetics.

[11]  N. Rosenthal,et al.  A caudorostral wave of RALDH2 conveys anteroposterior information to the cardiac field , 2003, Development.

[12]  M. Shaw,et al.  Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation. , 2003, American journal of human genetics.

[13]  E. Haan,et al.  Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation. , 2003, American journal of human genetics.

[14]  S. Bhattacharya,et al.  A locus for isolated cataract on human Xp , 2002, Journal of medical genetics.

[15]  P. Chambon,et al.  Embryonic retinoic acid synthesis is essential for heart morphogenesis in the mouse. , 2001, Development.

[16]  T. Evans,et al.  Anterior endoderm is sufficient to rescue foregut apoptosis and heart tube morphogenesis in an embryo lacking retinoic acid. , 2000, Developmental biology.

[17]  P. Sieving,et al.  Identification and characterization of the human homologue (RAI2) of a mouse retinoic acid-induced gene in Xp22. , 1999, Genomics.

[18]  D. Grafham,et al.  Characterization of SCML1, a new gene in Xp22, with homology to developmental polycomb genes. , 1998, Genomics.

[19]  A. Toutain,et al.  Mental retardation in Nance-Horan syndrome: clinical and neuropsychological assessment in four families. , 1997, American journal of medical genetics.

[20]  Michael Denis Higgins,et al.  The Nance‐Horan syndrome: a rare X‐linked ocular‐dental trait with expression in heterozygous females , 1984, Clinical genetics.