TY - JOUR
T1 - Definition of 5q11.2 microdeletion syndrome reveals overlap with CHARGE syndrome and 22q11 deletion syndrome phenotypes
AU - Snijders Blok, Charlotte
AU - Corsten-Janssen, Nicole
AU - Fitzpatrick, David R.
AU - Romano, Corrado
AU - Fichera, Marco
AU - Vitello, Girolamo Aurelio
AU - Willemsen, Marjolein H.
AU - Schoots, Jeroen
AU - Pfundt, Rolph
AU - van Ravenswaaij-Arts, Conny M A
AU - Hoefsloot, Lies
AU - Kleefstra, Tjitske
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Microdeletions of the 5q11.2 region are rare; in literature only two patients with a deletion in this region have been reported so far. In this study, we describe four additional patients and further define this new 5q11.2 microdeletion syndrome. A comparison of the features observed in all six patients with overlapping 5q11.2 deletions showed a phenotypic spectrum that overlaps with CHARGE syndrome and 22q11.2 deletion syndrome including choanal atresia, developmental delay, heart defects, external ear abnormalities, and short stature. No colobomas or abnormalities of semicircular canals and olfactory nerves were reported. Two male patients had genital abnormalities. We estimated a 2.0Mb (53.0-55.0Mb) Shortest Region of Overlap (SRO) for the main clinical characteristics of the syndrome. This region contains nine genes and two non-coding microRNAs. In this region DHX29 serves as the candidate gene as it encodes an ATP-dependent RNA-helicase that is involved in the initiation of RNA translation. Screening a small cohort of 14 patients who presented the main features, however, did not reveal any pathogenic abnormalities of DHX29.
AB - Microdeletions of the 5q11.2 region are rare; in literature only two patients with a deletion in this region have been reported so far. In this study, we describe four additional patients and further define this new 5q11.2 microdeletion syndrome. A comparison of the features observed in all six patients with overlapping 5q11.2 deletions showed a phenotypic spectrum that overlaps with CHARGE syndrome and 22q11.2 deletion syndrome including choanal atresia, developmental delay, heart defects, external ear abnormalities, and short stature. No colobomas or abnormalities of semicircular canals and olfactory nerves were reported. Two male patients had genital abnormalities. We estimated a 2.0Mb (53.0-55.0Mb) Shortest Region of Overlap (SRO) for the main clinical characteristics of the syndrome. This region contains nine genes and two non-coding microRNAs. In this region DHX29 serves as the candidate gene as it encodes an ATP-dependent RNA-helicase that is involved in the initiation of RNA translation. Screening a small cohort of 14 patients who presented the main features, however, did not reveal any pathogenic abnormalities of DHX29.
KW - 22q11.2 deletion syndrome
KW - 5q11.2 microdeletion syndrome
KW - CHARGE syndrome
KW - Choanal atresia
KW - DHX29
KW - Intellectual disability
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U2 - 10.1002/ajmg.a.36680
DO - 10.1002/ajmg.a.36680
M3 - Article
C2 - 25251717
AN - SCOPUS:84910594695
VL - 164
SP - 2843
EP - 2848
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 11
ER -