PMID- 37081310
OWN - NLM
STAT- MEDLINE
DCOM- 20230608
LR  - 20230608
IS  - 1552-4833 (Electronic)
IS  - 1552-4825 (Linking)
VI  - 191
IP  - 7
DP  - 2023 Jul
TI  - Parallel deletion and duplication at 7q11.23 in a silent carrier for two 
      reciprocal syndromic disorders.
PG  - 1849-1857
LID - 10.1002/ajmg.a.63215 [doi]
AB  - Partial deletions at chromosome 7q11.23 are causative for the autosomal-dominant 
      Williams-Beuren syndrome (WBS), whereas the partial duplication of this region 
      leads to the 7q11.23 duplication syndrome. Both syndromes are highly penetrant 
      and occur with a frequency of 1:7500-10,000 (WBS) and 1:13,000-20,000 (7q11.23 
      duplication syndrome). They are associated with multiple organ defects, 
      intellectual disability, and typical facial dysmorphisms showing broad phenotypic 
      variability. The 7q11.23 region is susceptible to chromosomal rearrangements due 
      to flanking segmental duplications and regions of long repetitive DNA segments. 
      Here, we report on a family with two children affected by WBS and clinically 
      unaffected parents. Interestingly, metaphase fluorescence in situ hybridization 
      (FISH) revealed a deletion on 7q11.23 in the father. Intensive genetic testing, 
      using interphase FISH, whole genome sequencing and optical genome mapping led to 
      the confirmation of a 1.5 Mb deletion at one 7q11.23 allele and the 
      identification of a reciprocal 1.8 Mb duplication at the other allele. This 
      finding is highly important regarding genetic counseling in this family. The 
      father is a silent carrier for two syndromic disorders, thus his risk to transmit 
      a disease-causing allele is 100%. To the best of our knowledge we, here, report 
      on the first case in which the phenotype of a microdeletion/microduplication 
      syndrome was compensated by its reciprocal counterpart.
CI  - (c) 2023 The Authors. American Journal of Medical Genetics Part A published by 
      Wiley Periodicals LLC.
FAU - Luhmann, Jonathan Lukas
AU  - Luhmann JL
AUID- ORCID: 0000-0002-9446-2411
AD  - Hannover Medical School, Department of Human Genetics, Hannover, Germany.
FAU - Schmidt, Gunnar
AU  - Schmidt G
AD  - Hannover Medical School, Department of Human Genetics, Hannover, Germany.
FAU - Auber, Bernd
AU  - Auber B
AD  - Hannover Medical School, Department of Human Genetics, Hannover, Germany.
FAU - Bergmann, Anke Katharina
AU  - Bergmann AK
AD  - Hannover Medical School, Department of Human Genetics, Hannover, Germany.
FAU - Brandau, Oliver
AU  - Brandau O
AD  - SYNLAB MVZ Humangenetik Mannheim GmbH, Mannheim, Germany.
FAU - Louis, Anja
AU  - Louis A
AD  - Labor fur Humangenetische Diagnostik, Mannheim, Germany.
FAU - Hentze, Sabine
AU  - Hentze S
AD  - Labor fur Humangenetische Diagnostik, Mannheim, Germany.
FAU - Eisfeld, Katrin
AU  - Eisfeld K
AD  - Labor fur Humangenetische Diagnostik, Mannheim, Germany.
FAU - Schlegelberger, Brigitte
AU  - Schlegelberger B
AD  - Hannover Medical School, Department of Human Genetics, Hannover, Germany.
FAU - Klaes, Ruediger
AU  - Klaes R
AD  - SYNLAB MVZ Humangenetik Mannheim GmbH, Mannheim, Germany.
FAU - Steinemann, Doris
AU  - Steinemann D
AD  - Hannover Medical School, Department of Human Genetics, Hannover, Germany.
LA  - eng
PT  - Journal Article
DEP - 20230420
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
SB  - IM
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Williams Syndrome/genetics
MH  - Genetic Testing
MH  - Phenotype
MH  - Chromosome Aberrations
MH  - Chromosomes, Human, Pair 7/genetics
MH  - Chromosome Deletion
OTO - NOTNLM
OT  - 7q11.23 duplication
OT  - Williams-Beuren syndrome
OT  - genetic counselling
OT  - optical genome mapping
OT  - phenotypical rescue
OT  - silent carrier
EDAT- 2023/04/21 00:42
MHDA- 2023/06/08 06:42
CRDT- 2023/04/20 23:32
PHST- 2023/04/06 00:00 [revised]
PHST- 2023/02/27 00:00 [received]
PHST- 2023/04/07 00:00 [accepted]
PHST- 2023/06/08 06:42 [medline]
PHST- 2023/04/21 00:42 [pubmed]
PHST- 2023/04/20 23:32 [entrez]
AID - 10.1002/ajmg.a.63215 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2023 Jul;191(7):1849-1857. doi: 10.1002/ajmg.a.63215. Epub 2023 
      Apr 20.