Genetics and genetic counselling: An introduction
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
Figure 1.1 shows the main symbols used in constructing pedigrees. The symbols shown for the sexes (□, ○) are preferred to the alternatives (♂, ♀), which tend to be confused at a distance. Heterozygous carriers can be denoted by half-shaded symbols or, in the case of an X-linked disorder, by a central dot. Although the sign for an early abortion (spontaneous or induced) can also be used for a stillbirth, it is preferable to denote the sex of the latter with an appropriate symbol and indicate beneath the symbol that it was a stillbirth. The previous use of a broken line for an offspring from an outside marriage is no longer appropriate, as ‘illegitimacy’ is no longer a meaningful concept in most Western societies. However, employing a broken line in a pedigree is still useful to represent the situation where parentage is unknown or unacknowledged or a relationship has broken down.
Fabry disease
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
The gene for α-galactosidase has been localized to Xq22.1 [11]. X-linked inheritance was first established by pedigree analysis (Figure 87.6). Two populations of cells – one with normal galactosidase activity and the other defective – were shown by cloning of cultured fibroblasts [54]. The cDNA for the gene for α-galactosidase has been cloned and sequenced [12], and this has permitted delineation of the nature of a number of mutations. The gene has seven exons. Major gene rearrangement detected by Southern hybridization included five deletions and duplication [55]. A number of smaller deletions and insertions have been identified, many of which led to frameshifts and premature termination. Most mutations in Fabry hemizygotes are not detected in this way. Mutations altering the processing of the mRNA transcript have been observed. Single nucleotide missense mutations have been identified in a majority of families [55–57], and most have been found only in one single family. However, a high frequency of mutation was observed at 14 CpG dinucleotides in the coding sequence. More than 300 mutations have been found in patients with Fabry disease [58]. Among them two novel mutations, 1277delAA (del2) and 1284delACTT(del4) in the 3ʹ terminus, obliterated the termination codon and generated multiple transcripts, most of them inactive [58]. Among 110 patients [50] the mutations were 76 percent missense 16 nonsenses and 3 percent each frameshift and splice site.
Development of palliative medicine in the United Kingdom and Ireland
Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita in Textbook of Palliative Medicine and Supportive Care, 2015
Although there are rapid changes occurring in the genetics and genomics fields, the primary tool of the genetic counsellor is the careful construction of an extended family medical history. The scope of practice for genetic counsellors includes the taking of a four-or five-generation pedigree, verifying the history with medical records (when possible), and evaluating the pattern of inheritance that is seen in the family history. This serves to inform recommendations for genetic testing, the making of an accurate clinical diagnosis, and the identification of potentially at-risk family members. Genetic counsellors work with the affected patient and family to assess the personal and family history of disease, coordinate genetic testing when appropriate, and provide education, advocacy, and support. This includes linking families to appropriate medical specialists as well as patient support and advocacy organizations. Education for patients and families includes describing the natural history of the disease, what types of medical interventions are indicated, the mode of inheritance, reproductive options, and eligibility for clinical research studies.
Inherited retinal degeneration current genetics practices – a needs assessment
Published in Ophthalmic Genetics, 2020
Sydney Strait, Rebecca Loman, Lindsay Erickson, Meghan DeBenedictis
The desired population was ophthalmologists and optometrists who see patients with IRDs. The use of social media has its own limitations. There are approximately 18,000 (2012) ophthalmologist and 44,000 (2020) optometrists in the U.S (12,13). It is unclear how many of these individuals have and use a Twitter account, were reached by this method of dispersal, or how many of them see patients with IRDs. The survey population was limited in size and location of respondents, possibly leading to limited diversity potential. Additionally, the study did not measure the knowledge of genetics for the respondents. There were providers who indicated they take pedigrees, explain inheritance patterns, or order genetic testing. However, the study did not determine the accuracy of the genetics related practice.
Cytogenetic analysis of patients with primary amenorrhea in Eastern India
Published in Journal of Obstetrics and Gynaecology, 2018
Shaulee Ghosh, Sanchita Roy, Pritha Pal, Atreyee Dutta, Ajanta Halder
The study subjects included patients with PA referred (n = 150) for chromosomal analysis to the Cytogenetic outdoor Vivekananda Institute of Medical Sciences, Kolkata of India from January 2013 to December 2015. The study was carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments in humans. The study has been reviewed and approved by the Ethics Committee of Vivekananda Institute of Medical Sciences, Ramakrishna Mission Seva Pratishthan, Kolkata. An informed consent was taken from each patient as per the norms of Institutional Ethics Committee before sample collection. The age group of the subjects ranged from 14 to 35 years with a mean of 20.26 ± 4.12 years. Pedigrees with details were drawn and in depth clinical evaluation and clinical information were obtained from all the subjects. About 1–2 ml of heparinised peripheral venous blood sample was collected from each patient aseptically and each sample was given a unique laboratory number.
Novel frameshift mutation in NYX gene in a Russian family with complete congenital stationary night blindness
Published in Ophthalmic Genetics, 2019
Marianna E. Ivanova, Inna V. Zolnikova, Ketevan V. Gorgisheli, Dmitry S. Atarshchikov, Preetam Ghosh, Debmalya Barh
The pedigree shows an X-linked inheritance of the disease (Figure 1). All the male patients had absent or severely reduced dark adaptation since early childhood and myopic staphyloma. They showed preserved color vision, pale optic disc, thin and hypopigmented retina, normal macula, and vascular attenuation. While the younger siblings showed moderate myopia, the elder sibling exhibited high myopia. All the patients had a normal electroretinogram (ERG) a-wave, indicative of photoreceptor function, but lack of b-wave due to defects in ON-BC signaling. Although retinal dysfunction was observed, there was no severe retinal degeneration in these patients. The visual functions (BCVA best corrected visual acuity) of the proband were: OD = 20/200 (1.0 LogMAR) sph −6.12 = 20/70 (0.55 LogMAR) and OS = 20/200 sph −6.12 = 20/70. The elder brother of proband’s had BCVA OD = 20/400 (1.3 LogMAR) sph −19.0 = 20/100 (0.7 LogMAR) and OS = 20/320 (1.2 LogMAR) sph −16.0 = 20/70 (0.55 LogMAR). The two siblings had a very similar eye fundus picture (Figure 2). Both affected siblings had big myopic staphyloma, in contrast to their both sisters. Also, clear thinning of the retina was observed, but there were no symptoms of severe retinal degeneration. Foveal reflex was preserved. Proband’s sisters, mother, and father all had clinically normal dark adaptation, normal eye appearance, emmetropia (normal refraction), normal eye fundus, and preserved color vision (Supplementary Table S1).
Related Knowledge Centers
- Astigmatism
- Dwarfism
- Hair Loss
- Mendelian Inheritance
- Phenotype
- Proband
- Selective Breeding
- Zygosity
- Autosome
- X-Linked Recessive Inheritance