TY - JOUR
T1 - Clinical and molecular evaluation of 13 Brazilian patients with Gomez-López-Hernández syndrome
AU - Perrone, Eduardo
AU - Perez, Ana Beatriz Alvarez
AU - D'Almeida, Vânia
AU - de Mello, Claudia Berlim
AU - Jacobina, Marcela Amaral Avelino
AU - Loureiro, Rafael Maffei
AU - Burlin, Stênio
AU - Migliavacca, Michele
AU - do Amaral Virmond, Luiza
AU - Graziadio, Carla
AU - Pedroso, José Luiz
AU - Mendes, Elaine Lustosa
AU - Gomy, Israel
AU - de Macena Sobreira, Nara Lygia
N1 - Funding Information:
information National Human Genome Research Institute, Grant/Award Number: 1U54HG006542The authors would like to thank Joyce Lopes Yamamoto from the Universidade Federal de São Paulo and Viviane Nakano from GeneOne, DASA, for their help in the DNA extraction procedures; AFIP (Associação Fundo de Incentivo à Pesquisa) for their support in the DNA extraction procedures; Rafael Fabiano Machado Rosa, Vinicius de Freitas de Mattos, and Professor Paulo Ricardo Gazzola Zen from the Universidade Federal de Ciências da Saúde de Porto Alegre, and Rosenelle Oliveira Araújo Benício for helping to recruit the cohort for the study; Professor Orlando G. Barsottini and Victor Rebelo Procaci, from the Universidade Federal de São Paulo for help us with the neurological examination of one patient; Professor Decio Brunoni, from the Universidade Presbiteriana Mackenzie and Professor Silvia Bragagnolo, from the Universidade Federal de São Paulo for their help in the morphological examination of the patients; we would also like to thank Professor Gilberto de Castro Junior, from the Universidade de São Paulo and Professor Tulio Konstantyner, from Department of Pediatrics- Universidade Federal de São Paulo, for their help in the revision of this manuscript.
Publisher Copyright:
© 2020 Wiley Periodicals LLC.
PY - 2021/4
Y1 - 2021/4
N2 - We aim to characterize patients with Gomez-López-Hernández syndrome (GLHS) clinically and to investigate them molecularly. A clinical protocol, including a morphological and neuropsychological assessment, was applied to 13 patients with GLHS. Single-nucleotide polymorphism (SNP) array and whole-exome sequencing were undertaken; magnetic resonance imaging was performed in 12 patients, including high-resolution, heavily T2-weighted sequences (HRT2) in 6 patients to analyze the trigeminal nerves. All patients presented alopecia; two did not present rhombencephalosynapsis (RES); trigeminal anesthesia was present in 5 of the 11 patients (45.4%); brachycephaly/brachyturricephaly and mid-face retrusion were found in 84.6 and 92.3% of the patients, respectively. One patient had intellectual disability. HRT2 sequences showed trigeminal nerve hypoplasia in four of the six patients; all four had clinical signs of trigeminal anesthesia. No common candidate gene was found to explain GLHS phenotype. RES does not seem to be an obligatory finding in respect of GLHS diagnosis. We propose that a diagnosis of GLHS should be considered in patients with at least two of the following criteria: focal non-scarring alopecia, rhombencephalosynapsis, craniofacial anomalies (brachyturrycephaly, brachycephaly or mid-face retrusion), trigeminal anesthesia or anatomic abnormalities of the trigeminal nerve. Studies focusing on germline whole genome sequencing or DNA and/or RNA sequencing of the alopecia tissue may be the next step for the better understanding of GLHS etiology.
AB - We aim to characterize patients with Gomez-López-Hernández syndrome (GLHS) clinically and to investigate them molecularly. A clinical protocol, including a morphological and neuropsychological assessment, was applied to 13 patients with GLHS. Single-nucleotide polymorphism (SNP) array and whole-exome sequencing were undertaken; magnetic resonance imaging was performed in 12 patients, including high-resolution, heavily T2-weighted sequences (HRT2) in 6 patients to analyze the trigeminal nerves. All patients presented alopecia; two did not present rhombencephalosynapsis (RES); trigeminal anesthesia was present in 5 of the 11 patients (45.4%); brachycephaly/brachyturricephaly and mid-face retrusion were found in 84.6 and 92.3% of the patients, respectively. One patient had intellectual disability. HRT2 sequences showed trigeminal nerve hypoplasia in four of the six patients; all four had clinical signs of trigeminal anesthesia. No common candidate gene was found to explain GLHS phenotype. RES does not seem to be an obligatory finding in respect of GLHS diagnosis. We propose that a diagnosis of GLHS should be considered in patients with at least two of the following criteria: focal non-scarring alopecia, rhombencephalosynapsis, craniofacial anomalies (brachyturrycephaly, brachycephaly or mid-face retrusion), trigeminal anesthesia or anatomic abnormalities of the trigeminal nerve. Studies focusing on germline whole genome sequencing or DNA and/or RNA sequencing of the alopecia tissue may be the next step for the better understanding of GLHS etiology.
KW - Gomez-Lopéz-Hernández
KW - Rhombencephalosynapsis
KW - focal alopecia
KW - trigeminal anesthesia
KW - whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85098320582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85098320582&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.62059
DO - 10.1002/ajmg.a.62059
M3 - Article
C2 - 33381921
AN - SCOPUS:85098320582
SN - 1552-4825
VL - 185
SP - 1047
EP - 1058
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 4
ER -