Health as a Symbolic Media Interchanging between Body and Social System

Genetics of disease, diagnosis and treatmen

Emerging genomic disorders in mental retardation.

Contains fulltext : 88731.pdf (Publisher’s version ) (Open Access)Radboud Universiteit Nijmegen, 25 november 2010Promotor : Brunner, H.G. Co-promotor : Vries, L.B.A. de318 p

An adult female patient with ring chromosome 21: Behavioural phenotype and results of high-resolution molecular characterisation

Contains fulltext : 90684.pdf (publisher's version ) (Closed access)Objective: A female adult patient with mild to moderate mental retardation and minor dysmorphisms was referred for neuropsychiatric examination because of psychotic and autistic symptoms and impulsive behaviours. Methods: Standardized neuropsychiatric and neuropsychological assessment as well as detailed somatic and neurological examination was performed. For genetic analysis, karyotyping, whole genome array analysis, and high-resolution detailed analysis of chromosome 21 were carried through. Results: Karyotyping showed a de novo ring chromosome 21: 46,XX,der(21)r(21)(p11q22.3). High-resolution array analysis demonstrated a complex aberration consisting of an interstitial duplication in 21q21.1, an interstitial deletion in 21q22.2q22.3, an interstitial deletion in 21q22.3 and a terminal deletion of 21q22.3. Apart from mild dysmorphisms, visual and auditory impairments, and infertility, no somatic or neurological abnormalities were found. A formal psychiatric diagnosis could not be established. The behavioural problems and the supposed psychiatric symptoms could be related to her disharmonic social cognitive profile. The behaviour normalized after the patient returned to a stable and structured living environment. Conclusion: High-resolution micro-array analysis techniques are essential to substantiate the genotype-phenotype correlation in patients with r(21) and other genetic disorders. Moreover, the results of this study stress the importance of the recognition of alexithymia as a potential cause for behavioural problems and psychiatric symptoms in patients with mental retardation in general.7 p

Social motivation a relative strength in DYRK1A syndrome on a background of significant speech and language impairments

Speech and language impairments are commonly reported in DYRK1A syndrome. Yet, speech and language abilities have not been systematically examined in a prospective cohort study. Speech, language, social behaviour, feeding, and non-verbal communication skills were assessed using standardised tools. The broader health and medical phenotype was documented using caregiver questionnaires, interviews and confirmation with medical records. 38 individuals with DYRK1A syndrome (23 male, median age 8 years 3 months, range 1 year 7 months to 25 years) were recruited. Moderate to severe intellectual disability (ID), autism spectrum disorder (ASD), vision, motor and feeding impairments were common, alongside epilepsy in a third of cases. Speech and language was disordered in all participants. Many acquired some degree of verbal communication, yet few (8/38) developed sufficient oral language skills to rely solely on verbal communication. Speech was characterised by severe apraxia and dysarthria in verbal participants, resulting in markedly poor intelligibility. Those with limited verbal language (30/38) used a combination of sign and graphic augmentative and alternative communication (AAC) systems. Language skills were low across expressive, receptive, and written domains. Most had impaired social behaviours (25/29). Restricted and repetitive interests were most impaired, whilst social motivation was a relative strength. Few individuals with DYRK1A syndrome use verbal speech as their sole means of communication, and hence, all individuals need early access to tailored, graphic AAC systems to support their communication. For those who develop verbal speech, targeted therapy for apraxia and dysarthria should be considered to improve intelligibility and, consequently, communication autonomy

Denys-Drash syndrome and congenital diaphragmatic hernia: another case with the 1097G > A(Arg366His) mutation.

Congenital diaphragmatic hernia (CDH) is a disorder of the development of the lung and diaphragm and is associated with pulmonary hypoplasia and pulmonary hypertension. Denys-Drash syndrome (DDS) is a well-known syndrome caused by several different germline mutations in the WT1-gene. CDH in DDS is rare. We present the third case of CDH with clinical features of DDS and the same, rare Arg366His mutation in the WT1-gene, as reported in the other two known cases. This report provides additional evidence that WT1 mutations can result in diaphragmatic hernia

A de novo balanced t(2;6)(p15;p22.3) in a patient with West Syndrome disrupts a lnc-RNA.

Contains fulltext : 110552.pdf (publisher's version ) (Closed access)In a male patient with West Syndrome we identified a perfectly balanced, de novo balanced translocation 46,XY,t(2;6)(p15;p22.3). No known protein coding genes were disrupted by the translocation and positional effects on nearby genes were excluded by expression studies. A putative long non-coding RNA, BX118339, spans the breakpoint on chromosome 6. It can be hypothesized that disruption of this non-coding transcript plays a role in the pathogenesis of the patient.1 mei 201

A microduplication of the Rubinstein-Taybi region on 16p13.3 in a girl with a bilateral complete cleft lip and palate and severe mental retardation.

Contains fulltext : 110796.pdf (Publisher’s version ) (Closed access)1 oktober 201

Tall stature and minor facial dysmorphisms in a patient with a 17.5 Mb interstitial deletion of chromosome 13 (q14.3q21.33): clinical report and review.

Contains fulltext : 53509.pdf (publisher's version ) (Closed access)We present a 4-year-old boy with developmental delay and several into minor dysmorphic features due to an interstitial deletion of 17.5 Mb on the long arm of chromosome 13 [46,XY,del (13)(q14.3q21.33)]. The deletion was detected initially during routine cytogenetic screening and further analyzed on a genome-wide BAC array. In contrast to several previous papers reporting a short stature, our patient was tall with a 1 year advanced skeletal age. In this paper, we compare growth and clinical features of this patient with previously reported cases, with a similar interstitial deletion on the long arm of chromosome 13

Cantu Syndrome Resulting from Activating Mutation in the KCNJ8 Gene

Item does not contain fulltextATP-sensitive potassium (KATP ) channels, composed of inward-rectifying potassium channel subunits (Kir6.1 and Kir6.2, encoded by KCNJ8 and KCNJ11, respectively) and regulatory sulfonylurea receptor (SUR1 and SUR2, encoded by ABCC8 and ABCC9, respectively), couple metabolism to excitability in multiple tissues. Mutations in ABCC9 cause Cantu syndrome (CS), a distinct multiorgan disease, potentially via enhanced KATP channel activity. We screened KCNJ8 in an ABCC9 mutation-negative patient who also exhibited clinical hallmarks of CS (hypertrichosis, macrosomia, macrocephaly, coarse facial appearance, cardiomegaly, and skeletal abnormalities). We identified a de novo missense mutation encoding Kir6.1[p.Cys176Ser] in the patient. Kir6.1[p.Cys176Ser] channels exhibited markedly higher activity than wild-type channels, as a result of reduced ATP sensitivity, whether coexpressed with SUR1 or SUR2A subunits. Our results identify a novel causal gene in CS, but also demonstrate that the cardinal features of the disease result from gain of KATP channel function, not from a Kir6-independent SUR2 function

The intellectual disability-associated CAMK2G p.Arg292Pro mutation acts as a pathogenic gain-of-function

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