TY - JOUR
T1 - A comprehensive molecular study identified 12 complementation groups with 56 novel FANC gene variants in Indian Fanconi anemia subjects
AU - George, Merin
AU - Solanki, Avani
AU - Chavan, Niranjan
AU - Rajendran, Aruna
AU - Raj, Revathi
AU - Mohan, Sheila
AU - Nemani, Sandeep
AU - Kanvinde, Shailesh
AU - Munirathnam, Deendayalan
AU - Rao, Sudha
AU - Radhakrishnan, Nita
AU - Lashkari, Harsha Prasada
AU - Ghildhiyal, Radha Gulati
AU - Manglani, Mamta
AU - Shanmukhaiah, Chandrakala
AU - Bhat, Sunil
AU - Ramesh, Sowmyashree
AU - Cherian, Anchu
AU - Junagade, Pritesh
AU - Vundinti, Babu Rao
N1 - Funding Information:
We would like to thank all the patients for participating in our study. We also thank the pediatricians and hemato‐oncologists for the clinical assessment of the FA patients. We thank Prof. Alan D'Andrea (Dana‐Farber Cancer Institute, Boston, USA) for his guidance to conduct Fanconi anemia research in our Institute. Thanks also due to Dr. Chandrasekharappa Settara (NIH/NHGRI, Bethesda, USA) for his comments and suggestions on our manuscript. This study was funded by DST/SERB (Grant Number EEQ/2016/000510; B. R. V).
Publisher Copyright:
© 2021 Wiley Periodicals LLC
PY - 2021/12
Y1 - 2021/12
N2 - Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer. There has been a discovery of 22 FANC genes known to be involved in the FA pathway. This wide number of pathway components makes molecular diagnosis challenging for FA. We present here the most comprehensive molecular diagnosis of FA subjects from India. We observed a high frequency (4.42 ± 1.5 breaks/metaphase) of chromosomal breakages in 181 FA subjects. The major clinical abnormalities observed were skin pigmentation (70.2%), short stature (46.4%), and skeletal abnormalities (43.1%), along with a few minor clinical abnormalities. The combination of Sanger sequencing and Next Generation Sequencing could molecularly characterize 164 (90.6%) FA patients and identified 12 different complementation groups [FANCA (56.10%), FANCG (16.46%), FANCL (12.80%), FANCD2 (4.88%), FANCJ (2.44%), FANCE (1.22%), FANCF (1.22%), FANCI (1.22%), FANCN (1.22%), FANCC (1.22%), FANCD1 (0.61%) and FANCB (0.61%)]. A total of 56 novel variants were identified in our cohort, including a hotspot variant: a deletion of exon 27 in the FANCA gene and a nonsense variant at c.787 C>T in the FANCG gene. Our comprehensive molecular findings can aid in the stratification of molecular investigation in the diagnosis and management of FA patients.
AB - Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer. There has been a discovery of 22 FANC genes known to be involved in the FA pathway. This wide number of pathway components makes molecular diagnosis challenging for FA. We present here the most comprehensive molecular diagnosis of FA subjects from India. We observed a high frequency (4.42 ± 1.5 breaks/metaphase) of chromosomal breakages in 181 FA subjects. The major clinical abnormalities observed were skin pigmentation (70.2%), short stature (46.4%), and skeletal abnormalities (43.1%), along with a few minor clinical abnormalities. The combination of Sanger sequencing and Next Generation Sequencing could molecularly characterize 164 (90.6%) FA patients and identified 12 different complementation groups [FANCA (56.10%), FANCG (16.46%), FANCL (12.80%), FANCD2 (4.88%), FANCJ (2.44%), FANCE (1.22%), FANCF (1.22%), FANCI (1.22%), FANCN (1.22%), FANCC (1.22%), FANCD1 (0.61%) and FANCB (0.61%)]. A total of 56 novel variants were identified in our cohort, including a hotspot variant: a deletion of exon 27 in the FANCA gene and a nonsense variant at c.787 C>T in the FANCG gene. Our comprehensive molecular findings can aid in the stratification of molecular investigation in the diagnosis and management of FA patients.
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U2 - 10.1002/humu.24286
DO - 10.1002/humu.24286
M3 - Article
AN - SCOPUS:85116384324
SN - 1059-7794
JO - Human Mutation
JF - Human Mutation
ER -