Informing a value care model: lessons from an integrated adult neurogenomics clinic.

Background: Advances in genomics provide improved opportunities for diagnosis of complex neurogenetic disorders, yet the optimal approach to translate these benefits to the outpatient clinic is unclear.

Aims: We retrospectively reviewed referral indications and outcomes of an integrated multidisciplinary team (MDT) clinic pathway for adults with suspected neurogenetic disorders. The associated cost implications were estimated.

A novel synonymous KMT2B variant in a patient with dystonia causes aberrant splicing.

Background: Heterozygous KMT2B variants are a common cause of dystonia. A novel synonymous KMT2B variant, c.5073C>T (p.

Investigation of current models of care for genetic heart disease in Australia: A national clinical audit.

Background: This sub-study of the Australian Genomics Cardiovascular Genetic Disorders Flagship sought to conduct the first nation-wide audit in Australia to establish the current practices across cardiac genetics clinics.

Method: An audit of records of patients with a suspected genetic heart disease (cardiomyopathy, primary arrhythmia, autosomal dominant congenital heart disease) who had a cardiac genetics consultation between 1st January 2016 and 31 July 2018 and were offered a diagnostic genetic test.

Results: This audit included 536 records at multidisciplinary cardiac genetics clinics from 11 public tertiary hospitals across five Australian states.

Multisystem Progeroid Syndrome With Lipodystrophy, Cardiomyopathy, and Nephropathy Due to an p.R349W Variant.

Background: Pathogenic variants in lamin A/C () cause a variety of progeroid disorders including Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, and atypical progeroid syndrome. Six families with 11 patients harboring a pathogenic heterozygous c.1045C>T; p.

KBG syndrome presenting with brachydactyly type E.

We report the case of a young woman who presented at age 10 years with height on the tenth centile, brachydactyly type E and mild developmental delay. Biochemistry and hormonal profiles were normal. Differential diagnoses considered included Albright hereditary osteodystrophy without hormone resistance (a.

Understanding the expectations of patients with inherited retinal dystrophies.

Background: UK genetic ophthalmology services for patients with retinal dystrophy (RD) are variable. Little research exists to define service requirements, or expectations, of patients and their families. This study aimed to explore the views and perceived benefits of genetic ophthalmology services among members of families with RD.

Understanding the impact of genetic testing for inherited retinal dystrophy.

The capability of genetic technologies is expanding rapidly in the field of inherited eye disease. New genetic testing approaches will deliver a step change in the ability to diagnose and extend the possibility of targeted treatments. However, evidence is lacking about the benefits of genetic testing to support service planning.

Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy.

We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous KIF11 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. Subsequent Sanger sequencing of KIF11 in a further 15 unrelated microcephalic probands with lymphedema and/or chorioretinopathy identified additional heterozygous mutations in 12 of them.

Retinal structure, function, and molecular pathologic features in gyrate atrophy.

Purpose: To describe phenotypic variability and to report novel mutational data in patients with gyrate atrophy.

Design: Retrospective case series.

Participants: Seven unrelated patients (10 to 52 years of age) with clinical and biochemical evidence of gyrate atrophy.

Unilateral vitelliform maculopathy: a comprehensive phenotype study with molecular screening of BEST1 and PRPH2.

Aim: To describe the clinical features of a case series of patients with unilateral vitelliform maculopathy and the results of screening BEST1 and PRPH2 for disease-causing mutations.

Design/methods: This was a retrospective case series study of six patients ascertained over a 2-year period. Ophthalmological examination, fundus photography, autofluorescence imaging, optical coherence tomography and detailed electrophysiological assessment were undertaken.

A phenotypic study of congenital stationary night blindness (CSNB) associated with mutations in the GRM6 gene.

Purpose: To describe the clinical phenotype and the molecular pathology in a group of patients with congenital stationary night blindness due to mutations in GRM6, a gene encoding the ON bipolar metabotropic glutamate receptor 6 (mGluR6).

Methods: Nine patients from seven families (age range, 7-75; median, 10 years) with a clinical diagnosis of autosomal recessive complete congenital stationary night blindness were ascertained. Clinical examination, imaging and electrophysiological assessment were performed.

A survey of DNA variation of C2ORF71 in probands with progressive autosomal recessive retinal degeneration and controls.

Purpose: Mutations of C2ORF71 have recently been reported to be associated with autosomal recessive (AR) retinitis pigmentosa (RP) in humans and with visual defects in zebrafish. C2ORF71 is located on 2p23.2 and encodes a 1288-amino-acid protein of unknown function, predominately expressed in the photoreceptors.

X-linked cone dystrophy caused by mutation of the red and green cone opsins.

X-linked cone and cone-rod dystrophies (XLCOD and XLCORD) are a heterogeneous group of progressive disorders that solely or primarily affect cone photoreceptors. Mutations in exon ORF15 of the RPGR gene are the most common underlying cause. In a previous study, we excluded RPGR exon ORF15 in some families with XLCOD.

A detailed phenotypic assessment of individuals affected by MFRP-related oculopathy.

Purpose: To determine the spectrum of mutations and phenotypic variability within patients with mutations in membrane-type frizzled related protein gene (MFRP).

Methods: Individuals were initially ascertained based on a phenotype similar to that previously published in association with MFRP mutations. Affected patients underwent a full ophthalmic examination (best-corrected visual acuity, slit-lamp examination, applanation tonometry, and fundoscopy), color fundus photography, optical coherence tomography, autofluorescence imaging, and electrophysiology.

Recessive mutations of the gene TRPM1 abrogate ON bipolar cell function and cause complete congenital stationary night blindness in humans.

Complete congenital stationary night blindness (cCSNB) is associated with loss of function of rod and cone ON bipolar cells in the mammalian retina. In humans, mutations in NYX and GRM6 have been shown to cause the condition. Through the analysis of a consanguineous family and screening of nine additional pedigrees, we have identified three families with recessive mutations in the gene TRPM1 encoding transient receptor potential cation channel, subfamily M, member 1, also known as melastatin.

Familial breast cancer: double heterozygosity for BRCA1 and BRCA2 mutations with differing phenotypes.

The co-existence of mutations in the BRCA1 and BRCA2 genes is unusual, and to date almost all cases reported have had at least one of the Ashkenazi founder mutations. We report on a family in whom individuals are double heterozygotes for a mutation in BRCA1 and a novel splice site mutation in BRCA2. The phenotypes are discordant, where one sister has had multiple cancers in the BRCA spectrum, while the other is unaffected at 65 years of age.