Clinical findings and a DNA methylation signature in kindreds with alterations in ZNF711.

ZNF711 is one of eleven zinc-finger genes on the X chromosome that have been associated with X-linked intellectual disability. This association is confirmed by the clinical findings in 20 new cases in addition to 11 cases previously reported. No consistent growth aberrations, craniofacial dysmorphology, malformations or neurologic findings are associated with alterations in ZNF711.

Qualitative Olfactory Disorders: Patient Experiences and Self-Management.

Background: Qualitative olfactory disorders in the form of parosmia and phantosmia are very subjective and cannot be measured at present. They pose an unpleasant experience for patients and a therapeutic challenge for clinicians.

Objective: This study aimed to characterise the specific experiences of patients affected by the qualitative symptoms of parosmia and phantosmia including both triggers for symptoms and self-help measures they have tried.

Barriers to effective health care for patients who have smell or taste disorders.

Objectives: Smell/taste disturbances are a common but underrated, under-researched and under treated sensory loss and an independent risk factor for reduced longevity. This study aimed to characterise the experience of patients with these disorders in seeking help.

Design: The study was designed by patients together with clinicians through a dedicated workshop and conducted as a cross-sectional survey to capture experiences in public and private healthcare settings internationally.

Constraint and conservation of paired-type homeodomains predicts the clinical outcome of missense variants of uncertain significance.

The need to interpret the pathogenicity of novel missense variants of unknown significance identified in the homeodomain of X-chromosome aristaless-related homeobox (ARX) gene prompted us to assess the utility of conservation and constraint across these domains in multiple genes compared to conventional in vitro functional analysis. Pathogenic missense variants clustered in the homeodomain of ARX contribute to intellectual disability (ID) and epilepsy, with and without brain malformation in affected males. Here we report novel c.

STAC3 variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility.

SH3 and cysteine-rich domain-containing protein 3 (STAC3) is an essential component of the skeletal muscle excitation-contraction coupling (ECC) machinery, though its role and function are not yet completely understood. Here, we report 18 patients carrying a homozygous p.(Trp284Ser) STAC3 variant in addition to a patient compound heterozygous for the p.

Successful pregnancies and reduced treatment requirement while breast feeding in a patient with congenital hypoparathyroidism due to homozygous c.68C>A null parathyroid hormone gene mutation.

A female patient with consanguineous parents presented at the age of 4 with isolated hypoparathyroidism due to a parathyroid hormone (PTH) gene mutation. She was managed with alfacalcidol and calcium supplements, and developed normally. Her consanguineous parents described symptoms suggestive of hypocalcaemia but had normal serum calcium and low normal PTH levels.

A retrospective audit of the characteristics and treatment outcomes in patients with diabetes-related charcot neuropathic osteoarthropathy.

Aims: To review the characteristics, management and outcomes one year after diagnosis in patients with diabetes related charcot neuropathic osteoarthropathy (CN) treated at the Diabetes Podiatry service, Waitemata District Health Board (WDHB) between 2000-2014.

Methods: Patients with diabetes and recorded diagnosis of CN were identified from the podiatry service records. Clinical details were retrospectively obtained from WDHB databases and patient medical records.

Management of Rabies Prophylaxis for Potential Bat Exposures in a Level III Neonatal Intensive Care Unit.

This report describes the unique challenges of managing potential exposure to bats in a neonatal intensive care unit. The outcome demonstrates that rabies post-exposure prophylaxis can be safely administered to preterm infants with evidence that preterm infants are able to develop adequate titers post vaccination. Infect Control Hosp Epidemiol 2017;38:483-485.

Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis.

DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS.

An evaluation of the impact of memory and mood on antiepileptic drug adherence.

Rationale: Antiepileptic drugs are the mainstay of treatment for patients with epilepsy. Adherence to the prescribed regimen is a major factor in achieving a reduced seizure burden, which can decrease morbidity and mortality. Patients with epilepsy oftentimes complain about difficulty with memory.

Delineation of the 3p14.1p13 microdeletion associated with syndromic distal limb contractures.

Distal limb contractures (DLC) represent a heterogeneous clinical and genetic condition. Overall, 20-25% of the DLC are caused by mutations in genes encoding the muscle contractile apparatus. Large interstitial deletions of the 3p have already been diagnosed by standard chromosomal analysis, but not associated with a specific phenotype.

Mutations in NOTCH1 cause Adams-Oliver syndrome.

Notch signaling determines and reinforces cell fate in bilaterally symmetric multicellular eukaryotes. Despite the involvement of Notch in many key developmental systems, human mutations in Notch signaling components have mainly been described in disorders with vascular and bone effects. Here, we report five heterozygous NOTCH1 variants in unrelated individuals with Adams-Oliver syndrome (AOS), a rare disease with major features of aplasia cutis of the scalp and terminal transverse limb defects.

FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair.

Chronic kidney disease (CKD) represents a major health burden. Its central feature of renal fibrosis is not well understood. By exome sequencing, we identified mutations in FAN1 as a cause of karyomegalic interstitial nephritis (KIN), a disorder that serves as a model for renal fibrosis.

Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus-specific database.

Renal coloboma syndrome, also known as papillorenal syndrome is an autosomal-dominant disorder characterized by ocular and renal malformations. Mutations in the paired-box gene, PAX2, have been identified in approximately half of individuals with classic findings of renal hypoplasia/dysplasia and abnormalities of the optic nerve. Prior to 2011, there was no actively maintained locus-specific database (LSDB) cataloguing the extent of genetic variation in the PAX2 gene and phenotypic variation in individuals with renal coloboma syndrome.

Familial mental retardation due to a cryptic subtelomeric translocation -del 14qter and dup 9qter (the Anyon phenotype).

An example of familial mental retardation is described in which there is a distinctive phenotype. It consists of IQ in the 30-50 range, microcephaly, short stature, narrow skull, prominent ears and nose and a cryptic subtelomeric translocation resulting in del 14qter and dup 9qter. Variable features include congenital heart disease, peripheral neuropathy and epilepsy.

Floating-Harbor syndrome complicated by tethered cord: a new association and potential contribution from growth hormone therapy.

Floating-Harbor syndrome is a rare syndrome with short stature, severely delayed bone age, typical facies and delay in expressive speech. Structural malformations are uncommon, and tethered cord or other forms of spinal dysraphism have not previously been reported. We report on a case of Floating-Harbor syndrome, complicated by tethered cord and discuss the possibility that growth hormone therapy may contribute to the development of symptoms of this malformation.

De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency.

Both nuclear and mitochondrial DNA mutations can cause energy generation disorders. Respiratory chain complex I deficiency is the most common energy generation disorder and a frequent cause of infantile mitochondrial encephalopathies such as Leigh's disease and lethal infantile mitochondrial disease. Most such cases have been assumed to be caused by nuclear gene defects, but recently an increasing number have been shown to be caused by mutations in the mitochondrially encoded complex I subunit genes ND4, ND5, and ND6.

Bio-social origins of depression in the community. Interactions between social adversity, cortisol and serotonin neurotransmission.

Background: Social adversity may be a risk factor for depression, by increasing cortisol secretion, which impairs serotonin (5-HT) neurotransmission.

Aims: To examine this causal pathway in a community setting.

Method: Women who were currently ICD-10 depressed (n=94), vulnerable to depression but not depressed (n=166) and non-vulnerable controls (n=177) were recruited.

Separate and combined effects of methylphenidate and behavior modification on boys with attention deficit-hyperactivity disorder in the classroom.

This study evaluated the separate and combined effects of behavior modification and 2 doses of methylphenidate (MPH; 0.3 and 0.6 mg/kg) compared with baseline (no behavior modification and a placebo) on the classroom behavior and academic performance of 31 ADHD (attention deficit-hyperactivity disorder) boys attending a summer treatment program.