title: Congenital methemoglobinemia caused by Hb-MRatnagiri (beta-63CAT-->TAT, His-->Tyr) in an Indian family.
abstract: Hb-M is a very rare hemoglobinopathy in the Indian subcontinent. We report a family with Hb-M with lifelong cyanosis from the Ratnagiri district in western India. The propositus was a 11-year-old female child with a history of increasing cyanosis exacerbated by fever and weakness. Similar complaints were also noted in her mother and five maternal family members. There was no history of cardiac illness or exposure to drugs and chemicals. The methemoglobin level was 39.3% in the propositus and 21.1% in her mother with normal NADH-methemoglobin reductase activity. Abnormal absorption peaks by spectroscopic analysis, presence of hemoglobin instability, and a slow-moving band on starch gel electrophoresis supported the presence of Hb-M. Automated DNA sequence analysis of the beta globin gene showed a C-->T substitution at codon 63. This leads to a substitution of histidine (CAT) by tyrosine (TAT) at the beta 63 (E7) position, similar to Hb-M Saskatoon. We have named this variant as Hb-M(Ratnagiri).
authors.affiliation: Institute of Immunohaematology, Indian Council of Medical Research, K.E.M. Hospital, Parel, Mumbai 400012, India.
authors.forename: Prabhakar S
authors.initials: PS
authors.lastname: Kedar
authors.forename: Anita H
authors.initials: AH
authors.lastname: Nadkarni
authors.forename: Supriya
authors.initials: S
authors.lastname: Phanasgoankar
authors.forename: Manisha
authors.initials: M
authors.lastname: Madkaikar
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.forename: Ajit C
authors.initials: AC
authors.lastname: Gorakshakar
authors.forename: Roshan B
authors.initials: RB
authors.lastname: Colah
authors.forename: Dipika
authors.initials: D
authors.lastname: Mohanty
mesh_terms: D019943:Amino Acid Substitution; D002648:Child; D002908:Chronic Disease; D003490:Cyanosis / Q000151:congenital / Q000209:etiology / Q000235:genetics; D003596:Cytosine; D004247:DNA / Q000235:genetics; D005260:Female; D005914:Globins / Q000235:genetics*; D006449:Hemoglobin M / Q000235:genetics*; D006639:Histidine; D006801:Humans; D007194:India; D008708:Methemoglobinemia / Q000150:complications / Q000151:congenital*; D010375:Pedigree; D013941:Thymine; D014443:Tyrosine
chemical_list: C502787:hemoglobin M(Ratnagiri); D014443:Tyrosine; D006639:Histidine; D003596:Cytosine; D005914:Globins; D004247:DNA; D006449:Hemoglobin M; D013941:Thymine