Current carrier screening methods do not identify a proportion of carriers that may have children affected by spinal muscular atrophy (SMA). Additional genetic data is essential to inform accurate risk assessment and genetic counselling of SMA carriers. This study aims to quantify the various genotypes among parents of children with SMA.
A retrospective cohort study was undertaken at Sydney Children\'s Hospital Network, the major SMA referral centre for New South Wales, Australia. Participants included children with genetically confirmed SMA born between 2005 and 2021. Data was collected on parent genotype inclusive of copy number of SMN1 exons 7 and 8. The number of SMN2 exon 7 copies were recorded for the affected children. Descriptive statistics were used to determine the proportion of carriers of 2+0 genotype classified as silent carriers. Chi-square test was used to correlate the association between parents with a heterozygous SMN1 exon 7 deletion and two copies of exon 8 and ≥3 SMN2 copy number in the proband.
SMA carrier testing was performed in 118/154 (76.6%) parents, incorporating 59 probands with homozygous SMN1 deletions and one proband with compound heterozygote pathogenic variants. Among parents with a child with SMA, 7.6% had two copies of SMN1 exon 7. When only probands with a homozygous SMN1 exon 7 deletion were included, 6.9% of parents had two copies of SMN1 exon 7. An association was observed between heterozygous deletion of SMN1 exon 7 with two copies of exon 8 in a parent and ≥3 SMN2 copy number in the affected proband (p = 0.07).
This study confirmed a small but substantial proportion of silent carriers not identified by conventional screening within an Australian context. Accordingly, the effectiveness of carrier screening for SMA is linked with genetic counselling to enable health literacy regarding high and low risk results and is complemented by new-born screening and maintaining clinical awareness for SMA. Gene conversion events may underpin the associations between parent carrier status and proband SMN2 copy number.

Partial deletions at chromosome 7q11.23 are causative for the autosomal-dominant Williams-Beuren syndrome (WBS), whereas the partial duplication of this region leads to the 7q11.23 duplication syndrome. Both syndromes are highly penetrant and occur with a frequency of 1:7500-10,000 (WBS) and 1:13,000-20,000 (7q11.23 duplication syndrome). They are associated with multiple organ defects, intellectual disability, and typical facial dysmorphisms showing broad phenotypic variability. The 7q11.23 region is susceptible to chromosomal rearrangements due to flanking segmental duplications and regions of long repetitive DNA segments. Here, we report on a family with two children affected by WBS and clinically unaffected parents. Interestingly, metaphase fluorescence in situ hybridization (FISH) revealed a deletion on 7q11.23 in the father. Intensive genetic testing, using interphase FISH, whole genome sequencing and optical genome mapping led to the confirmation of a 1.5 Mb deletion at one 7q11.23 allele and the identification of a reciprocal 1.8 Mb duplication at the other allele. This finding is highly important regarding genetic counseling in this family. The father is a silent carrier for two syndromic disorders, thus his risk to transmit a disease-causing allele is 100%. To the best of our knowledge we, here, report on the first case in which the phenotype of a microdeletion/microduplication syndrome was compensated by its reciprocal counterpart.

BACKGROUND: The value of repeated nasopharyngeal lavage (NPL) to detect silent carriers of Streptococcus equi has not been investigated.
OBJECTIVE: Determine if results of serial testing for S. equi by NPL predicts subsequent true carrier status as determined by both NPL and guttural pouch lavage.
METHODS: An outbreak of strangles with 100% morbidity in 41 mature Icelandic horses was followed prospectively to investigate development of silent carriers. All were initially positive to S. equi on NPL. The farm was closed to horse movement during the entire study.
METHODS: Prospective observational study. Testing for S. equi was performed by NPL at weeks 18, 28, 29, and 30 postindex case and subsequently at week 45 by both NPL and guttural pouch lavage. Carrier status at week 45 was compared to results obtained at weeks 18, 28, 29, and 30. Descriptive statistics were calculated. Comparisons were made using Fisher\'s exact test or the Freeman-Halton extension with a P < .05 level of significance.
RESULTS: Of 24 noncarriers at week 45, only 4 horses were negative on all 3 consecutive weekly NPL samples at weeks 28 to 30. However, 10 of the 11 horses with at least 3 negative NPL obtained from weeks 18, 28, 29, and 30 were S. equi-free at week 45 (P = .03).
CONCLUSIONS: Repeated NPL on at least 3 separate occasions can assist in predicting S. equi carrier-free status in horses after recovery from a strangles outbreak.

On Mar 11th, 2020, the World Health Organization (WHO) stated in its Situation Report - 51 Coronavirus disease 2019 (COVID-19) as a pandemic. In early April 2020, a teaching hospital underwent shutdown and quarantine due to an outbreak of infection in accordance with Section 6 of the Infection Protection Act (index patient and 5 infected nursing staff). The complete staff (physicians, nurses and nonmedical personnel [NMP]) underwent COVID-19 testing within two phases: (1) between Apr 3rd and 5th, 2020 [n=1170], followed by (2) between Apr 8th and 9th, 2020 [n=953] with COVID-19 silent carrier positivity rates in accordance to testing phases of (1) n=19 (1.6%) and (2) n=25 (2.6%). The cumulative infection rate for NMP (1.6%), doctors (3.8%) and nurses (9.7%) was connected to type and extent of COVID-19 patient contact. Despite COVID-19 positivity of 34.8% (46 of 132 beds), a risk-free management of hospital operation is possible to a certain extent if hygiene regulations and strict patient selection are followed. However, a COVID-19-free clinic cannot be expected due to silent carriers.

BACKGROUND: Individuals whose copies of the survival motor neuron 1 (SMN1) gene exist on the same chromosome are considered silent carriers for spinal muscular atrophy (SMA). Conventional screening for SMA only determines SMN1 copy number without any information regarding how those copies are arranged. A single nucleotide variant (SNV) rs143838139 is highly linked with the silent carrier genotype, so testing for this SNV can more accurately assess risk to a patient of having an affected child.
METHODS: Using a custom-designed SNV-specific Taqman genotyping assay, we determined and validated a model for silent-carrier detection in the laboratory.
RESULTS: An initial cohort of 21 pilot specimens demonstrated results that were 100% concordant with a reference laboratory method; this cohort was utilized to define the reportable range. An additional 177 specimens were utilized for a broader evaluation of clinical validity and reproducibility. Allelic-discrimination analysis demonstrated tight clustering of genotype groupings and excellent reproducibility, with a coefficient of variation for all genotypes ranging from 1% to 4%.
CONCLUSIONS: The custom-developed Taqman SNV genotyping assay we tested provides a rapid, accurate, and cost-effective method for routine SMA silent-carrier screening and considerably improves detection rates of residual risk for SMA carriers.

BACKGROUND: Genes for thalassaemia, haemoglobin S, Glucose-6-phosphate dehydrogenase which confer resistance to malaria are found in high frequencies in Nigeria, 25% of the population being carriers of the sickle cell trait while another 25% are hemizygous for the G6PD gene. The frequency of alpha thalassaemia is equally high among Nigerians but there is little information on beta thalassaemia in this population. A recent study however suggest a high prevalence of beta thalassaemia in the same population, hence the need for this study.
METHODS: Haemoglobin A(2) and HbF were determined in healthy adults who have haemoglobin A genotype by elution after electrophoresis and alkaline denaturation methods respectively.
RESULTS: The mean HbA(2) among the subjects was 3.3% (range 2.0-5.6%) while the mean HbF was 2.6% (range 0.4-8.8%). Twenty-six percent of the subjects had HbA(2) values higher than 3.9% while 86% had HbF values greater than 1%, twenty-four percent had elevated HbA(2) and HbF. The mean HbA(2) value was 2.7% among those with HbF <1%, 3.6% among those with HbF 1-3% and 3.1% among those with HbF >3%.
CONCLUSIONS: These findings confirm that the frequency of beta thalassaemia in western Nigeria is higher than previously thought and that many of the individuals studied may be silent carriers of the beta thalassaemia trait. Its presence may also have been masked by the high prevalence of alpha thalassaemia in the same environment. It is therefore important to consider beta thalassaemia trait as a differential diagnosis in patients who present with haemolytic anaemia in this environment.