Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome: Analysis of 13 patients with a de novo deletion

Dagmar Wieczorek; Mario Krause; Frank Majewski; Beate Albrecht; Denise Horn; Olaf Riess; Gabriele Gillessen-Kaesbach

doi:10.1038/sj.ejhg.5200498

Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome: Analysis of 13 patients with a de novo deletion

Dagmar Wieczorek^*, Mario Krause, Frank Majewski, Beate Albrecht, Denise Horn, Olaf Riess, Gabriele Gillessen-Kaesbach

^*Corresponding author for this work

Institute of Human Genetics

86 Citations (Scopus)

Abstract

We performed clinical, cytogenetic, and molecular analyses on 13 patients (8 females and 5 males, aged 6 months to 13 years) with Wolf-Hirschhorn syndrome due to de novo deletions of chromosome 4p. All patients presented with the typical facial gestalt, microcephaly, and profound mental retardation. Other clinical signs were low birth weight (10/13; 77%), postnatal short stature (8/12; 66%), muscular hypotonia (12/13; 92%), seizures (11/13; 85%), congenital heart defects (4/13; 31%), colobomata of iris (4/12; 33%), genital anomalies (4/13; 31%), deafness (3/13; 23%), and renal anomalies (3/13; 23%). The smallest deletion was a submicroscopic terminal deletion of nearly 2.5 Mb. The largest was a terminal deletion of nearly 30 Mb. Cleft lip/palate, preauricular pits/tags, and congenital heart defects were present only in patients with terminal deletions larger than 10 Mb. The deviations from mean birth weight, birth length, and postnatal head circumference correlated with the size of the deletion. Determining the parental origin of the deletion with microsatellite markers, the maternal allele was missing in three patients and the paternal allele in eight patients. Our observations support the existence of a partial genotype-phenotype correlation in Wolf-Hirschhorn syndrome.

Original language	English
Journal	European Journal of Human Genetics
Volume	8
Issue number	7
Pages (from-to)	519-526
Number of pages	8
ISSN	1018-4813
DOIs	https://doi.org/10.1038/sj.ejhg.5200498
Publication status	Published - 07.2000

Funding

We thank Professor Eberhard Passarge for continuous support and reading the manuscript, and Professor Bernhard Horsthemke for helpful discussion. In addition, we thank Barbara Henke, Barbara Ulrich, Elke Jürgens, and Gudrun Rodepeter for excellent technical assistance, and the parents for taking part in this study. We thank Dr Herdit Schüler for the results of previous chromosomal analysis in patient 1, Dr AJH Hamers for performing FISH with D4S10 in patient 2, and Dr JJM Engelen for FISH in patient 4. We also thank Tracy Wright for the cosmids pC847.351, 33c6, 21f12 and 228a7. In addition, we thank CEPH for providing the YACs. DW and GG-K were supported in part by a young investigators’ grant from the Medical Faculty, University of Essen (IFORES 107402.0), and by the Deutsche Forschungsgemeinschaft (Wi 1440/4-1).

Research Areas and Centers

Research Area: Medical Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.ejhg.5200498

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title = "Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome: Analysis of 13 patients with a de novo deletion",

abstract = "We performed clinical, cytogenetic, and molecular analyses on 13 patients (8 females and 5 males, aged 6 months to 13 years) with Wolf-Hirschhorn syndrome due to de novo deletions of chromosome 4p. All patients presented with the typical facial gestalt, microcephaly, and profound mental retardation. Other clinical signs were low birth weight (10/13; 77\%), postnatal short stature (8/12; 66\%), muscular hypotonia (12/13; 92\%), seizures (11/13; 85\%), congenital heart defects (4/13; 31\%), colobomata of iris (4/12; 33\%), genital anomalies (4/13; 31\%), deafness (3/13; 23\%), and renal anomalies (3/13; 23\%). The smallest deletion was a submicroscopic terminal deletion of nearly 2.5 Mb. The largest was a terminal deletion of nearly 30 Mb. Cleft lip/palate, preauricular pits/tags, and congenital heart defects were present only in patients with terminal deletions larger than 10 Mb. The deviations from mean birth weight, birth length, and postnatal head circumference correlated with the size of the deletion. Determining the parental origin of the deletion with microsatellite markers, the maternal allele was missing in three patients and the paternal allele in eight patients. Our observations support the existence of a partial genotype-phenotype correlation in Wolf-Hirschhorn syndrome.",

author = "Dagmar Wieczorek and Mario Krause and Frank Majewski and Beate Albrecht and Denise Horn and Olaf Riess and Gabriele Gillessen-Kaesbach",

note = "Funding Information: We thank Professor Eberhard Passarge for continuous support and reading the manuscript, and Professor Bernhard Horsthemke for helpful discussion. In addition, we thank Barbara Henke, Barbara Ulrich, Elke J{\"u}rgens, and Gudrun Rodepeter for excellent technical assistance, and the parents for taking part in this study. We thank Dr Herdit Sch{\"u}ler for the results of previous chromosomal analysis in patient 1, Dr AJH Hamers for performing FISH with D4S10 in patient 2, and Dr JJM Engelen for FISH in patient 4. We also thank Tracy Wright for the cosmids pC847.351, 33c6, 21f12 and 228a7. In addition, we thank CEPH for providing the YACs. DW and GG-K were supported in part by a young investigators{\textquoteright} grant from the Medical Faculty, University of Essen (IFORES 107402.0), and by the Deutsche Forschungsgemeinschaft (Wi 1440/4-1).",

year = "2000",

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doi = "10.1038/sj.ejhg.5200498",

language = "English",

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T1 - Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome: Analysis of 13 patients with a de novo deletion

AU - Wieczorek, Dagmar

AU - Krause, Mario

AU - Majewski, Frank

AU - Albrecht, Beate

AU - Horn, Denise

AU - Riess, Olaf

AU - Gillessen-Kaesbach, Gabriele

N1 - Funding Information: We thank Professor Eberhard Passarge for continuous support and reading the manuscript, and Professor Bernhard Horsthemke for helpful discussion. In addition, we thank Barbara Henke, Barbara Ulrich, Elke Jürgens, and Gudrun Rodepeter for excellent technical assistance, and the parents for taking part in this study. We thank Dr Herdit Schüler for the results of previous chromosomal analysis in patient 1, Dr AJH Hamers for performing FISH with D4S10 in patient 2, and Dr JJM Engelen for FISH in patient 4. We also thank Tracy Wright for the cosmids pC847.351, 33c6, 21f12 and 228a7. In addition, we thank CEPH for providing the YACs. DW and GG-K were supported in part by a young investigators’ grant from the Medical Faculty, University of Essen (IFORES 107402.0), and by the Deutsche Forschungsgemeinschaft (Wi 1440/4-1).

PY - 2000/7

Y1 - 2000/7

N2 - We performed clinical, cytogenetic, and molecular analyses on 13 patients (8 females and 5 males, aged 6 months to 13 years) with Wolf-Hirschhorn syndrome due to de novo deletions of chromosome 4p. All patients presented with the typical facial gestalt, microcephaly, and profound mental retardation. Other clinical signs were low birth weight (10/13; 77%), postnatal short stature (8/12; 66%), muscular hypotonia (12/13; 92%), seizures (11/13; 85%), congenital heart defects (4/13; 31%), colobomata of iris (4/12; 33%), genital anomalies (4/13; 31%), deafness (3/13; 23%), and renal anomalies (3/13; 23%). The smallest deletion was a submicroscopic terminal deletion of nearly 2.5 Mb. The largest was a terminal deletion of nearly 30 Mb. Cleft lip/palate, preauricular pits/tags, and congenital heart defects were present only in patients with terminal deletions larger than 10 Mb. The deviations from mean birth weight, birth length, and postnatal head circumference correlated with the size of the deletion. Determining the parental origin of the deletion with microsatellite markers, the maternal allele was missing in three patients and the paternal allele in eight patients. Our observations support the existence of a partial genotype-phenotype correlation in Wolf-Hirschhorn syndrome.

AB - We performed clinical, cytogenetic, and molecular analyses on 13 patients (8 females and 5 males, aged 6 months to 13 years) with Wolf-Hirschhorn syndrome due to de novo deletions of chromosome 4p. All patients presented with the typical facial gestalt, microcephaly, and profound mental retardation. Other clinical signs were low birth weight (10/13; 77%), postnatal short stature (8/12; 66%), muscular hypotonia (12/13; 92%), seizures (11/13; 85%), congenital heart defects (4/13; 31%), colobomata of iris (4/12; 33%), genital anomalies (4/13; 31%), deafness (3/13; 23%), and renal anomalies (3/13; 23%). The smallest deletion was a submicroscopic terminal deletion of nearly 2.5 Mb. The largest was a terminal deletion of nearly 30 Mb. Cleft lip/palate, preauricular pits/tags, and congenital heart defects were present only in patients with terminal deletions larger than 10 Mb. The deviations from mean birth weight, birth length, and postnatal head circumference correlated with the size of the deletion. Determining the parental origin of the deletion with microsatellite markers, the maternal allele was missing in three patients and the paternal allele in eight patients. Our observations support the existence of a partial genotype-phenotype correlation in Wolf-Hirschhorn syndrome.

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U2 - 10.1038/sj.ejhg.5200498

DO - 10.1038/sj.ejhg.5200498

M3 - Journal articles

C2 - 10909852

AN - SCOPUS:0033949022

SN - 1018-4813

VL - 8

SP - 519

EP - 526

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 7

ER -

Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome: Analysis of 13 patients with a de novo deletion

Abstract

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