Evaluation of two population screening programmes for founder mutations in the Australian Jewish community: a protocol paper.

Introduction: People of Ashkenazi Jewish (AJ) ancestry are more likely than unselected populations to have a pathogenic variant, which cause a significantly increased risk of breast, ovarian and prostate cancer. Three specific pathogenic variants, referred to as -Jewish founder mutations (B-JFM), account for >90% of pathogenic variants in people of AJ ancestry. Current practice of identifying eligible individuals for testing based on personal and/or family history has been shown to miss at least 50% of people who have one of these variants.

Genetics and pediatric hospital admissions, 1985 to 2017.

Purpose: To determine the prevalence and sociodemographic and hospitalization history of genetic conditions in a sample of inpatients in a pediatric hospital in 2017, and to compare results with unpublished studies from 1985, 1995, and 2007.

Methods: Two weeks of admissions were classified according to a pre-existing categorization, based on genetic etiology, encompassing chromosomal and monogenic conditions, multifactorial (MF) conditions, and no known genetic cause.

Results: In 2017, 299 (16%) patients had chromosomal or monogenic conditions, 6-7% more than 2007 and 1995, but similar to 1985.

Ashkenazi Jewish population screening for Tay-Sachs disease: the international and Australian experience.

Internationally, Tay-Sachs disease (TSD) preconception screening of Ashkenazi Jewish (AJ) individuals and couples has led to effective primary prevention of TSD. In Australia, adolescent preconception genetic screening programs operate mainly in Jewish community high schools. These existing programs offer an effective means of primary prevention of TSD, are cost effective and safe.

High school Tay-Sachs disease carrier screening: 5 to 11-year follow-up.

The Melbourne high school Tay-Sachs disease (TSD) carrier screening program began in 1997. The aim of this study was to assess the outcomes of this screening program among those who had testing more than 5 years ago, to evaluate the long-term impact of screening. A questionnaire was used for data collection and consisted of validated scales and purposively designed questions.

Tay Sachs disease in Australia: reduced disease incidence despite stable carrier frequency in Australian Jews.

Objectives: To evaluate the outcomes of preconception screening of Jewish Australians for Tay Sachs disease (TSD) carrier status on Jewish TSD-affected births.

Design, Participants And Setting: Epidemiological observational study involving a complete retrospective audit of infantile and intermediate TSD cases diagnosed in Sydney and Melbourne between 1 January 1995 and 31 December 2011 (Royal Children's Hospital Melbourne; Pacific Laboratory Medicine Services, Pathology North, NSW Health Pathology, Sydney; Victorian Clinical Genetics Services, Melbourne; and SA Pathology, Adelaide), and carrier frequency among Jewish high school students attending schools participating in TSD screening programs over the same period.

Main Outcome Measures: Jewish TSD carrier frequency; and expected versus observed Jewish TSD-affected births.

Population-based carrier screening for cystic fibrosis in Victoria: the first three years experience.

Background: Cystic fibrosis (CF) is the most common inherited, life-shortening condition affecting Australian children. The carrier frequency is one per 25 and most babies with CF are born to parents with no family history. Carrier testing is possible before a couple has an affected infant.

Two cases of trisomy 16 mosaicism ascertained postnatally.

Postnatally ascertained trisomy 16 mosaicism is a rare diagnosis, with only three reported cases to date with no defined clinical phenotype. Trisomy 16 mosaicism diagnosed prenatally is common and associated with variable pregnancy outcomes ranging from stillbirth with multiple congenital abnormalities to an apparently normal newborn, making the genetic counseling very challenging. It is not clear whether uniparental disomy (UPD) 16 contributes to the phenotype, although it has been suggested that maternal UPD 16 affects the rate of intra-uterine growth retardation (IUGR) and congenital anomalies.

Consumer contribution to the delivery of genetic health services.

Clinical genetics services have been the focus of evaluation and guidelines since the 1970s. In this study we used consumer satisfaction as the evaluative measure with the aim being to seek feedback from consumers of a genetics service to inform quality measures for client-centered genetic services. In the first phase of the study issues were identified by consumers and health professionals around delivering genetics services and the priorities ranked into five themes: expectations, information, respect, privacy and logistics.

Community-wide screening for cystic fibrosis carriers could replace newborn screening for the diagnosis of cystic fibrosis.

Most babies with cystic fibrosis (CF) are born to parents who did not know they were carriers until their baby was diagnosed with CF, usually by newborn screening. It is only after the birth of their first child with CF that couples are offered genetic counselling and reproductive choices. Most use this information for prenatal testing of subsequent pregnancies.

Keipert syndrome (Nasodigitoacoustic syndrome) is X-linked and maps to Xq22.2-Xq28.

Keipert syndrome is a rare condition comprising sensorineural deafness associated with facial and digital abnormalities. To date, Keipert syndrome has been reported in six male patients including two sib pairs; however the genetic basis of Keipert syndrome is yet to be elucidated. We report on the diagnosis of Keipert syndrome in the nephew of the brothers in the first report of Keipert syndrome, with a pedigree consistent with X-linked recessive inheritance.

Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency.

Background: Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder characterized by skeletal abnormalities such as hypoplasia of the mandible and clavicles and acro-osteolysis. Other features include cutaneous atrophy and lipodystrophy. Two genetic loci are known for MAD: lamin A/C (LMNA), encoding structural nuclear lamina proteins, and zinc metalloproteinase (ZMPSTE24), a membrane-bound endoprotease involved in post-translational proteolytic cleavage of carboxy terminal residues of prelamin A to form mature lamin A.

Determinants of preferences for genetic counselling in Jewish women.

Introduction: Patient preferences are central to the economic appraisal of health services. Cancer genetic services are relatively new, and little is known about clients' preferences. We sought to determine clients' preferences for genetic service delivery, and to identify factors that predict those preferences.

Distinctive collection of fetal anomalies: cleft lip and palate, multicystic dysplastic kidneys, 1-2 syndactyly, heterotopic olivary tissue and thymic hypoplasia.

A female fetus with an unusual collection of congenital anomalies was detected prenatally. The pregnancy was terminated at 21 weeks of gestation. Clinical and pathological findings of bilateral cleft lip and palate, micrognathia, thymic hypoplasia, unilateral 1-2 finger syndactyly, bilateral multicystic dysplastic kidneys and heterotopic olivary tissue are presented.

Delineation of facial archetypes by 3d averaging.

The objective of this study was to investigate the feasibility of creating archetypal 3D faces through computerized 3D facial averaging. A 3D surface scanner Fiore and its software were used to acquire the 3D scans of the faces while 3D Rugle3 and locally-developed software generated the holistic facial averages. 3D facial averages were created from two ethnic groups; European and Japanese and from children with three previous genetic disorders; Williams syndrome, achondroplasia and Sotos syndrome as well as the normal control group.

Tay Sachs disease carrier screening in schools: educational alternatives and cheekbrush sampling.

Purpose: Tay Sachs disease carrier screening programs have been offered successfully worldwide since 1970. The programs typically offer education, testing, and counseling to provide reproductive choices. One such program has been offered to Jewish school students in Melbourne since 1998.

A patient with monosomy 1p36, atypical features and phenotypic similarities with Cantu syndrome.

We report on a 16-year-old boy with a distal 1p36 deletion with some clinical features consistent with Cantu syndrome (OMIM#239850). He also has hypercholesterolemia, type II diabetes, recurrent bony fractures, and non-alcoholic steatohepatitis, not previously described in either condition. The 1p36 deletion was detected in a screen of all chromosome subtelomeres using multiplex ligation-dependent probe amplification and was verified using FISH with a region-specific BAC clone.

Log odds of carrying an Ancestral Mutation in BRCA1 or BRCA2 for a Defined personal and family history in an Ashkenazi Jewish woman (LAMBDA).

Introduction: Ancestral mutations in BRCA1 and BRCA2 are common in people of Ashkenazi Jewish descent and are associated with a substantially increased risk of breast and ovarian cancer. Women considering mutation testing usually have several personal and family cancer characteristics, so predicting mutation status from one factor alone could be misleading. The aim of this study was to develop a simple algorithm to estimate the probability that an Ashkenazi Jewish woman carries an ancestral mutation, based on multiple predictive factors.

Variable expression of campomelic dysplasia in a father and his 46, XY daughter.

Campomelic dysplasia (CD, MIM 114290) is characterised by widespread osseous abnormalities including bowing of the long bones, dysplasia of the cartilage of the tracheobronchial tree, and neurological abnormalities leading to high perinatal lethality. A majority of karyotypic males present as phenotypic females. The disorder has only recently been categorised as a dominantly transmitted entity after demonstration of heterozygous mutations in the SOX9 gene on chromosome 17q24.

Issues and concerns of couples presenting for preimplantation genetic diagnosis (PGD).

Background: The use of preimplantation genetic diagnosis (PGD) to select genetically 'normal' human embryos and to transfer them to the uterus of a woman has generated considerable controversy. Debate has occurred over the implications of PGD, sex selection, safety of embryonic manipulation and eugenics. This study evaluates a range of social and moral concerns of couples towards PGD and assisted reproductive technologies (ART) prior to treatment to obtain unbiased authentic attitudes independent of the treatment cycle and the outcome.