Molecular confirmation of germ line mosaicism for a submicroscopic deletion of chromosome 22q11

Hatchwell, Eli; Long, Fiona; Wilde, Jerry; Crolla, John A.; Temple, I. Karen

doi:10.1002/(sici)1096-8628(19980630)78:2<103::aid-ajmg1>3.0.co;2-p

Cited by 31 publications

(26 citation statements)

References 20 publications

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“…Furthermore, germline mosaicism for a submicroscopic del22q11.2 has been demonstrated in a mother who gave birth to two sibs with deletions and one unaffected baby (35). The mother found to be mosaic for the deletion was clinically normal (35). Interestingly, the unaffected sib was found to have inherited the same maternal haplotype at 22q11.2 in an undeleted form.…”

Section: Discussionmentioning

confidence: 98%

Spectrum of clinical variability in familial deletion 22q11.2: from full manifestation to extremely mild clinical anomalies

Digilio¹,

et al. 2003

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The 22q11.2 deletion (del22q11.2) syndrome is a genetic condition with wide interfamilial and intrafamilial variability in clinical expression. The aim of the present study was to review the prevalence of parental transmission in our series of patients with del22q11.2, and to analyse clinical findings of the affected parents. Parental transmission of del22q11.2 in our series was 17.2% (15/87), with a preferential maternal transmission (10/15). One or more major features of del22q11.2 were found in all deleted parents, but one of the mothers showed extremely mild clinical anomalies. The present data demonstrate that it should be current policy to test both parents of patients with del22q11.2, irrespective of the parental phenotype, in view of the fact that extremely mild clinical features can be detected in parents of deleted patients. This would provide accurate genetic counselling to del22q11.2 families, as relatively asymptomatic parents must be advised of the 50% risk of transmitting the deletion in a subsequent pregnancy. Various genetic and non-genetic factors, including modifier genes at separate loci, mosaicism, unstable mutations, allelic variations at the haploid locus, chance and environmental interaction, can be hypothesized to be involved in variable clinical expression, even in the same family.

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Section: Discussionmentioning

confidence: 98%

Spectrum of clinical variability in familial deletion 22q11.2: from full manifestation to extremely mild clinical anomalies

Digilio¹,

et al. 2003

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“…This could be explained by genetic predisposition to deletions in some families or the presence of germline mosaicism, although independent de novo events in the same family cannot be excluded. [21][22][23] Neonatal hypocalcemia caused by hypoparathyroidism is one of the cardinal symptoms of 22q11DS. In our series, it was reported in only 43% of cases but may have been underestimated because blood calcium levels were tested only in symptomatic patients.…”

Section: Discussionmentioning

confidence: 99%

Clinical Features and Follow-Up in Patients with 22q11.2 Deletion Syndrome

Cancrini¹,

Puliafito²,

Digilio³

et al. 2014

The Journal of Pediatrics

126

136

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“…Germline mosaicism for intragenic deletions has been reported for several genetic disorders, including the 22q11.2 deletion. 21 In cases for which a deceased child with features suggestive of DGS/VCFS was not tested for the deletion, a careful evaluation of the parents for the presence of mild phenotypic features and 22q11.2 deletion testing is recommended. These parents may elect prenatal testing with the understanding that the interpretation of negative test results is limited.…”

Section: Indications For Prenatal Testingmentioning

confidence: 99%

Prenatal diagnosis of the 22q11.2 deletion syndrome

Driscoll

2001

Genetics in Medicine

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The development of fluorescence in situ hybridization (FISH)-and polymerase chain reaction (PCR)-based assays for the detection of deletions of chromosome 22q11.2 has enabled the medical community to offer couples at risk prenatal diagnostic testing. Current indications for testing include a previous child with a 22q11.2 deletion or DiGeorge/velocardiofacial syndrome, an affected parent with a 22q11.2 deletion, and in utero detection of a conotruncal cardiac defect. Antenatal knowledge of the deletion status provides couples and clinicians with an accurate diagnosis, prognostic information, and recurrence risk, which may assist couples with their reproductive decisions. However, there are limitations to prenatal testing, which should be reviewed prior to testing. Genetics The majority of patients with DiGeorge and velocardiofacial syndrome (DGS/VCFS) have large interstitial deletions of chromosomal region 22q11.2. 1 In addition, several studies have demonstrated that a significant percentage of cardiac patients with conotruncal cardiac malformations have a 22q11.2 deletion. 2-5 Although DGS/VCFS were initially considered rare disorders, recent studies suggest that the 22q11.2 deletion may occur as frequently as 1 in 4000 live births. 6 Deletions of 22q11.2 have also been detected in patients with conotruncal anomaly face syndrome and in some patients with OpitzG/ BBB and Cayler cardiofacial syndrome. 7-9 These disorders, collectively referred to as the 22q11.2 deletion syndrome, are predominantly characterized by congenital cardiac defects, immune deficiencies secondary to aplasia or hypoplasia of the thymus, hypocalcemia due to small or absent parathyroid glands, palatal and speech abnormalities, and cognitive difficulties. Large clinical studies and case reports have shown that the phenotypic features seen in patients with the 22q11.2 deletion are much more variable and extensive than previously recognized, and include developmental problems, feeding difficulties, neurologic, ocular, psychiatric, renal, and skeletal abnormalities. 10 -13 Although the majority of deletions are de novo, the deletion can be transmitted as an autosomal dominant; hence, individuals with a 22q11.2 deletion have a 50% risk of having an affected offspring in each pregnancy. Familial deletions have been identified in 8 -28% of probands. 11,12 The development of fluorescence in situ hybridization (FISH)-and polymerase chain reaction (PCR)-based assays for the detection of deletions of chromosome 22q11.2 has enabled the medical community to offer couples at risk prenatal diagnostic testing. 14 -20 INDICATIONS FOR PRENATAL TESTINGCurrent indications for prenatal testing for the 2q11.2 deletion include (1) a previous child with a 22q11.2 deletion or DiGeorge/velocardiofacial syndrome, (2) an affected parent with a 22q11.2 deletion, and (3) in utero detection of a fetus with a conotruncal cardiac defect. The risk for unaffected parents of having another child with the 22q11.2 deletion is presumably low; however, prenatal testing for the de...

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Molecular confirmation of germ line mosaicism for a submicroscopic deletion of chromosome 22q11

Cited by 31 publications

References 20 publications

Spectrum of clinical variability in familial deletion 22q11.2: from full manifestation to extremely mild clinical anomalies

Spectrum of clinical variability in familial deletion 22q11.2: from full manifestation to extremely mild clinical anomalies

Clinical Features and Follow-Up in Patients with 22q11.2 Deletion Syndrome

Prenatal diagnosis of the 22q11.2 deletion syndrome

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