Taken together, the UBE2A deficiency syndrome in male patients with a mutation in or a deletion of UBE2A is characterized by ID, absent speech, seizures, urogenital anomalies, frequently including a small penis, and skin abnormalities, which include generalized hirsutism, low posterior hairline, myxedematous appearance, widely spaced nipples, and hair whorls.
Genotype-phenotype analysis confirmed that ZFHX1B deletions and stop mutations result in a recognizable facial dysmorphism with associated severe mental retardation and variable malformations such as Hirschsprung disease and congenital heart defects.
A novel missense mutation of the L1CAM gene (Xq28) is described in an adult patient affected with severe mental retardation, spastic paraparesis, adducted thumbs, agenesis of corpus callosum and microcephaly (L1 disease).
Because the DMD gene is located at Xp21.2, which is one breakpoint of the inv(X), and because its defects are rarely associated with severe mental retardation, the other clinical features of this patient were deemed likely to be associated with the opposite breakpoint at Xq22.
To test the applicability of this DNA delivery system for the correction of phenylketonuria, a metabolic disorder that causes severe mental retardation in children, we have delivered the human phenylalanine hydroxylase (PAH) gene to hepatocytes derived from a PAH-deficient mouse strain and demonstrated complete reconstitution of enzymatic activity.
Mowat-Wilson syndrome (MOWS) is caused by de novo heterozygous mutation at ZEB2 (SIP1, ZFHX1B) gene, and exhibit moderate to severe intellectual disability (ID), a characteristic facial appearance, epilepsy and other congenital anomalies.
Common clinical features associated with ATRX mutations include severe mental retardation, characteristic facial anomalies and variable degrees of urogenital defects and alpha-thalassemia.
Variants in IQSEC2 cause moderate to severe intellectual disability in males and a variable phenotype in females because this gene escapes from X-chromosome inactivation.
Hundreds of L1CAM gene mutations have been shown to be associated with congenital hydrocephalus, severe intellectual disability, aphasia, and motor symptoms.
Complete skipping of exon 66 due to novel mutations of the dystrophin gene was identified in two Japanese families of Duchenne muscular dystrophy with severe mental retardation.
We report on patients with heterozygous defects in CNTNAP2 or NRXN1 associated with severe intellectual disability, which has only been reported for recessive defects before.
Mutations in ATRX give rise to characteristic developmental abnormalities including severe mental retardation, facial dysmorphism, urogenital abnormalities and alpha-thalassaemia.
X-linked intellectual disability type Nascimento (XIDTN), caused by mutations in ubiquitin-conjugating enzyme E2A (UBE2A) gene, is characterized by moderate to severe intellectual disability, impaired speech, urogenital anomalies, skin abnormalities, and dysmorphic facial features.
We report on patients with heterozygous defects in CNTNAP2 or NRXN1 associated with severe intellectual disability, which has only been reported for recessive defects before.
Whereas the established synaptic role of NRXN1 suggests that synaptic defects contribute to the associated neuropsychiatric disorders and to severe MR as reported here, evidence for a synaptic role of the CNTNAP2-encoded protein CASPR2 has so far been lacking.
X linked lissencephaly and subcortical band heterotopia (XLIS/SBH) is a disorder of cortical development, which causes classical lissencephaly with severe mental retardation and epilepsy in hemizygous males and SBH associated with milder mental retardation and epilepsy in heterozygous females.
Additionally, a putatively causal point mutation in ZSWIM6 has been identified in several cases of acromelic frontonasal dysostosis with severe intellectual disability.
Christianson syndrome (CS) is caused by mutations in SLC9A6 and is characterized by severe intellectual disability, absent speech, microcephaly, ataxia, seizures, and behavioral abnormalities.
Although the patients with TSC2 mutations tend to exhibit relatively severe mental retardation in comparison to those with TSC1 mutations, a genotype-phenotype correlation could not yet be established.
Mutations in the CDKL5 gene (also known as STK9) have recently been shown to cause early onset epilepsy and severe mental retardation (ISSX or West syndrome).