Canadian College of Medical Geneticists (CCMG) points to consider: resuming genetic services in a pandemic-a summary.

The COVID-19 pandemic has disrupted the provision of genetic care in Canada. With the public health effort to flatten the curve, many clinics have moved to virtual care for select populations of patients while triaging and postponing others. As genetic services are asked to gradually resume, a roadmap is needed to ensure clinical care decisions for at-risk patients are transparent and equitable, that postponed care is resumed and that patients with or waiting for a genetic diagnosis are not disproportionately affected or abandoned.

Heterozygous intragenic deletions of FREM1 are not associated with trigonocephaly.

Recessive mutations in FRAS1-related extracellular matrix 1 (FREM1) are associated with two rare genetic disorders, Manitoba-oculo-tricho-anal (MOTA) and bifid nose with or without anorectal and renal anomalies (BNAR). Fraser syndrome is a more severe disorder that shows phenotypic overlap with both MOTA and anorectal and renal anomalies and results from mutations in FRAS1, FREM2 and GRIP1. Heterozygous missense mutations in FREM1 were reported in association with isolated trigonocephaly with dominant inheritance and incomplete penetrance.

PWS/AS MS-MLPA Confirms Maternal Origin of 15q11.2 Microduplication.

The proximal region of the long arm of chromosome 15q11.2-q13 is associated with various neurodevelopmental disorders, including Prader-Willi (PWS) and Angelman (AS) syndromes, autism, and other developmental abnormalities resulting from deletions and duplications. In addition, this region encompasses imprinted genes that cause PWS or AS, depending on the parent-of-origin.

A-TWinnipeg: Pathogenesis of rare ATM missense mutation c.6200C>A with decreased protein expression and downstream signaling, early-onset dystonia, cancer, and life-threatening radiotoxicity.

We studied 10 Mennonite patients who carry the c.6200C>A missense mutation (p.A2067D) in the ATM gene, all of whom exhibited a phenotypic variant of ataxia-telangiectasia (A-T) that is characterized by early-onset dystonia and late-onset mild ataxia, as previously described.

Understanding the impact of 1q21.1 copy number variant.

Background: 1q21.1 Copy Number Variant (CNV) is associated with a highly variable phenotype ranging from congenital anomalies, learning deficits/intellectual disability (ID), to a normal phenotype. Hence, the clinical significance of this CNV can be difficult to evaluate.

Inversion and deletion of 16q22 defined by array CGH, FISH, and RT-PCR in a patient with AML.

Acute myelomonocytic leukemia with eosinophilia is commonly associated with pericentric inversions of chromosome 16, involving the core binding factor beta gene (CBFB) on 16q22 and the myosin heavy chain gene (MYH11) on 16p13. The inv(16)(p13q22) results in a fusion gene comprising the 5'CBFB gene and the 3'MYH11 gene on the short arm of chromosome 16. The fusion gene interferes with the normal transcription of the CBFA/CBFB heterodimer and disrupts myeloid differentiation.

Ataxia-telangiectasia: atypical presentation and toxicity of cancer treatment.

Background: The onset of progressive cerebellar ataxia in early childhood is considered a key feature of ataxia-telangiectasia (A-T), accompanied by ocular apraxia, telangiectasias, immunodeficiency, cancer susceptibility and hypersensitivity to ionizing radiation.

Methods: We describe the clinical features and course of three Mennonite children who were diagnosed with A-T following the completion of therapy for lymphoid malignancies.

Results: Prior to cancer therapy, all had non-progressive atypical neurological abnormalities, with onset by age 30 months, including dysarthria, dyskinesia, hypotonia and/or dystonia, without telangiectasias.

Prenatal cytogenetic assessment and inv(2)(p11.2q13).

Objectives: To present a series of prenatally detected cases of recurrent pericentric inversions with euchromatic breakpoints and to review the literature to determine whether parental karyotyping is required for genetic counselling.

Methods: Cases of recurrent pericentric inversions with euchromatic breakpoints were collected from Canadian Cytogenetic Laboratories. Cases included inversions for chromosome 1(p13q21), chromosome 2(p11.

Congenital indifference to pain and deletion of chromosome 10q-: new association.

We describe a case of a de novo terminal deletion of the long arm of chromosome 10 with the novel feature of congenital indifference to pain in a 2-year 10-month-old boy. Relative indifference to pain defined by a lack of emotional response to pain has not been described previously in association with the terminal deletion of the long arm of chromosome 10.

Severe hemihypotrophy in a female infant with mosaic Turner syndrome: a variant of Russell-Silver syndrome?

Russell-Silver syndrome is a genetically heterogeneous condition. For most affected individuals, it represents a phenotype rather than a specific disorder. Although chromosomal anomalies, imprinting disorder, maternal uniparental disomy 7 as well as familial autosomal dominant and X-linked forms have been reported, the diagnosis remains determined on clinical grounds.