TY - JOUR

T1 - Exome sequencing reveals the first intragenic deletion in ABCA5 underlying autosomal recessive hypertrichosis

AU - Raza, Rubab

AU - Ullah, Asmat

AU - Haider, Nighat

AU - Krishin, Jai

AU - Shah, Muqadar

AU - Khan, Fati Ullah

AU - Abdullah, null

AU - Hansen, Torben

AU - Raza, Syed Irfan

AU - Ahmad, Wasim

AU - Basit, Sulman

N1 - Publisher Copyright: © 2022 British Association of Dermatologists.

PY - 2022

Y1 - 2022

N2 - Background: Hereditary hypertrichosis (HH) is characterized by excessive hair growth on various body areas, which is independent of the individual's age. This rare hair disorder has been classified by its origin (genetic or acquired), age of onset, breadth of hair distribution (universal or localized) and the affected body areas. HH is often linked to several additional congenital abnormalities involving teeth, heart and bones. Human HH is associated with heterozygous genomic duplications and deletions in the chromosomal region 17q24.2–q24.3, containing genes such as ABCA5, ABCA6, ABCA10 and MAP2K6. Recently, a homozygous splice-site variant in ABCA5 has been reported to cause autosomal recessive congenital generalized hypertrichosis terminalis (CGHT; OMIM 135400). Aim: To investigate the clinical and genetic basis of autosomal recessive hypertrichosis in a large consanguineous Pakistani family. Methods: In the present study, we characterized a family of Pakistani origin segregating CGHT in an autosomal recessive pattern, using whole exome sequencing followed by Sanger sequencing. Results: We identified a novel 2-bp intragenic deletion [NM_172232.4(ABCA5);c.977_978delAT] causing a frameshift variant (p.His326ArgfsTer5) in ABCA5. Conclusions: To our knowledge, this is the first intragenic deletion in ABCA5 underlying CGHT. The findings further validate the involvement of ABCA5 in hair development. The study will facilitate genetic counselling of families carrying CGHT-related features in Pakistani and other populations.

AB - Background: Hereditary hypertrichosis (HH) is characterized by excessive hair growth on various body areas, which is independent of the individual's age. This rare hair disorder has been classified by its origin (genetic or acquired), age of onset, breadth of hair distribution (universal or localized) and the affected body areas. HH is often linked to several additional congenital abnormalities involving teeth, heart and bones. Human HH is associated with heterozygous genomic duplications and deletions in the chromosomal region 17q24.2–q24.3, containing genes such as ABCA5, ABCA6, ABCA10 and MAP2K6. Recently, a homozygous splice-site variant in ABCA5 has been reported to cause autosomal recessive congenital generalized hypertrichosis terminalis (CGHT; OMIM 135400). Aim: To investigate the clinical and genetic basis of autosomal recessive hypertrichosis in a large consanguineous Pakistani family. Methods: In the present study, we characterized a family of Pakistani origin segregating CGHT in an autosomal recessive pattern, using whole exome sequencing followed by Sanger sequencing. Results: We identified a novel 2-bp intragenic deletion [NM_172232.4(ABCA5);c.977_978delAT] causing a frameshift variant (p.His326ArgfsTer5) in ABCA5. Conclusions: To our knowledge, this is the first intragenic deletion in ABCA5 underlying CGHT. The findings further validate the involvement of ABCA5 in hair development. The study will facilitate genetic counselling of families carrying CGHT-related features in Pakistani and other populations.

U2 - 10.1111/ced.15128

DO - 10.1111/ced.15128

M3 - Journal article

C2 - 35150007

AN - SCOPUS:85126288642

VL - 47

SP - 1137

EP - 1143

JO - Transactions of the St. John's Hospital Dermatological Society

JF - Transactions of the St. John's Hospital Dermatological Society

SN - 0307-6938

IS - 6

ER -