McCune−Albright Syndrome
Dongyou Liu in Handbook of Tumor Syndromes, 2020
Reflecting a state of coexistence of genetically distinct cell populations in a single individual arising from a single fertilized egg as a consequence of post-zygotic genetic events, mosaicism may occur in somatic or germline cells (and referred to as somatic mosaicism or germline mosaicism). Somatic mosaicism may evolve from errors in replication of segments of or whole chromosome (chromosomal aneuploidy), copy-neutral reciprocal gains and losses (acquired uniparental disomy or loss of heterozygosity), changes in nuclear or mitochondrial DNA, point mutation, or spontaneous reversion of an existing DNA mutation. Whereas somatic mosaicism taking place in early development is associated with widespread disease, that in late development may be silent or induce limited disease. However, somatic mosaic mutations do not pass onto offspring. By contrast, germline mosaicism has no phenotypic consequences on an individual, but will pass onto offspring [1,12].
Patterns of Inheritance: Mendelian and Non-Mendelian
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
In some instances, a normal appearing parent can have more than one child affected with an autosomal dominant condition. A possible explanation may be germline mosaicism whereby a parent carries the autosomal dominant disease-causing gene in some percentage of their germ cells, but not in their somatic cells. Because the disease-causing gene is only present in the germ cells the parent is not affected with the condition but can pass the condition on to his or her children. Obviously, germline mosaicism has significant implications for recurrence risks in a family and for genetic counseling.
McCune–Albright Syndrome
Dongyou Liu in Tumors and Cancers, 2017
Mosaicism occurring in somatic cells is known as somatic mosaicism. Somatic mosaic mutation may be clinically silent or may affect a portion of the body but will not pass to offspring. Whereas somatic mosaic mutations that take place early in development may cause widespread disease, those taking place late in development show limited disease. On the contrary, mosaicism occurring in germline cells is known as germline mosaicism. Although germline mosaicism does not have phenotypic consequences on an individual, it will pass to offspring.
Parental germline mosaic transmission of 5p13.2 microduplication in two siblings of a Chinese family
Published in Journal of Obstetrics and Gynaecology, 2022
Qi Tian, Li-Li Xu, Dong-Zhi Li
When two or more affected offsprings are born to apparently unaffected parents, germline mosaicism is suspected; however, this event will usually be neglected when only one offspring has been affected (Mohrenweiser and Zingg 1995). The ignorance of germline mosaicism may lead to the recurrence of diseases, as evidenced by the present study. Paternal germline mosaicism can be diagnosed by molecular investigation of sperm DNA. Diagnosis of maternal germline mosaicism, however, is not feasible because oocytes cannot be obtained. The present study has important implications for genetic counselling. For apparently a de novo case of microduplication, the potential for recurrence in future pregnancies should be discussed. Considering the great economic and psychological pressure brought by the duplication in the present family, preimplantation genetic testing (PGT) was recommended for future pregnancies.
Mutation of GALNTL5 gene identified in patients diagnosed with asthenozoospermia
Published in Human Fertility, 2020
Jun Hagiuda, Nobuyoshi Takasaki, Mototsugu Oya, Hiromichi Ishikawa, Hisashi Narimatsu
Detection of the mutation in only a certain percentage of the patient’s sperm could be attributed to germline mosaicism. This suggests that the sperm carrying the mutation would be differentiated from mutated spermatogonial stem cells and that they might arise in an early primordial germ cell or in one of their immediate precursors. We speculate that spermatogonial stem cells harbouring the mutation underwent apoptosis, because apoptosis occurs in more than half of differentiating spermatogonia during spermatogenesis and apoptotic spermatogenic cells are phagocytosed by Sertoli cells (Hai et al., 2014; Nakanishi & Shiratsuchi, 2004). The intercellular bridges in spermatogenesis allow passage of many molecules and organelles between germ cells (Greenbaum, Iwamori, Buchold, & Matzuk, 2011; Ventela, Toppari, & Parvinen, 2003). In our previous study, aberrant localization of the ubiquitin–proteasome system components were observed in the spermatozoa of hetero-mutant mice (Takasaki et al., 2014). We speculate that the connections via the intercellular bridges between differentiating spermatids arising from spermatogonia carrying the mutation, affected the abnormality rate among mature spermatozoa.
Germline mosaicism in a DMD family: incidental identification in prenatal diagnosis
Published in Journal of Obstetrics and Gynaecology, 2018
Germline mosaicism can occur with any inheritance pattern, but it is most commonly observed in autosomal dominant and X-linked disorders (Edwards 1989). A mosaic germline mutation is significant because it can be obscurely passed to offspring. Most individuals are unaware of a naturally occurring germline mutation until they have a child who is affected. Duchenne Muscular Dystrophy (DMD) is a severe X-linked neuromuscular disease with an incidence of approximately 1 in 3500 newborn boys. The DMD locus has a high mutation frequency: one-third of mutations are de novo, and two-thirds are inherited from carrier mothers (Lee et al. 2014). Instances of germinal mosaicism have been elucidated in DMD families on the basis of more than one affected offspring born to an apparently non-carrier parent (Bermúdez-López et al. 2014). Here we report on germline mosaicism in a DMD family incidentally identified in prenatal diagnosis by using chromosomal microarray analysis (CMA).
Related Knowledge Centers
- Allele
- Epigenetics
- Germline
- Germline Mutation
- Methylation
- Osteogenesis Imperfecta
- Somatic Cell
- Gamete
- Mosaic
- Duchenne Muscular Dystrophy