Genetic Disorders and the Fetus. Группа авторов

stroke, psychiatric problems, cognitive impairments, and dementia. Although CADASIL is mostly adult onset, we have provided prenatal diagnosis for a family with an affected young father, as noted earlier.

      Given the history of a previously affected offspring with a genetic disorder, the preconception visit serves as an ideal time to refocus on any putative diagnosis (or lack thereof), to check constantly updated databases where prior alterations are or are not considered pathogenic, and to perform newly available mutation analyses when applicable.

      Recognition of genotype–phenotype associations remains challenging for reasons that include expressivity, penetrance, multiple causal genes, modifier alleles, compound heterozygosity, locus heterogeneity, interacting polymorphisms of small effect, and digenic inheritance. For the vast majority of monogenic disorders, even without known epigenetic influence (such as epilepsy, microcephaly, holoprosencephaly, hydrocephalus, craniosynostosis), definitive genotype–phenotype associations remain unknown.

      Somatic mosaicism

We are all somatic postzygotic mosaics, either born that way or later as a consequence of spontaneously occurring mutations during our lifetimes. Using single‐cell whole‐genome sequencing of B lymphocytes, Zhang et al.⁸⁶⁶ found that the number of somatic mutations increases from <500 per cell in newborns to >3,000 per cell in centenarians. These dynamic changes involving other tissues as well, are likely to be associated with cancer and aging,⁸⁶⁷ and many disorders (Table 1.8).

Table 1.8 Selected examples of monogenic disorders with established somatic mosaicism with DNA confirmation.

Disorder	Gene	Reference
Achondrogenesis type 2	COL2A1	885
Aicardi–Goutières syndrome	TREX1	886
Alport syndrome	COL4A5	887
Alzheimer disease, early‐onset	PS1	888
Androgen insensitivity	AR	888
Atelostegenesis type I	FLNB	889
Beta‐propeller protein‐associated neurodegeneration	WDR45	890
Campomelic dysplasia	SOX9	888
Catecholaminergic polymorphic ventricular tachycardia	RYR2	891
Centronuclear myopathy	DNM2	892
Charcot–Marie–Tooth disease type 1E	PMP22	893
CHARGE syndrome	CHD7	888
Chronic infantile neurologic, cutaneous, articular syndrome	NLRP3	894 , 895
Chronic intestinal pseudo‐obstruction	ACTG2	864
Cleidocranial dysplasia	RUNX2	888
COL2A1 disorders	COL2A1	896
Congenital central hypoventilation syndrome	PHOX2B	897
Congenital contractural arachnodactyly	FBN2	888
Congenital disorder of glycosylation	SLC35A2	898
Congenital lipomatous overgrowth with vascular, epidermal and skeletal anomalies	PIK3CA	899
Cornelia de Lange syndrome	CdLS	900
Costello syndrome	HRAS	901
Creutzfeldt–Jakob disease	PRNP	902
Crouzon syndrome	FGFR2	903
Duchenne muscular dystrophy	DMD	888 , 904
Ectrodactyly	SHFM3	905
EEC (ectrodactyly, ectodermal dysplasia, and orofacial clefts)	P63	888
Epidermal nervus, rhabdomyosarcoma, Скачать книгу В начало < 51 52 53 54 55 56 57 58 59 60 > В конец