A novel mutation of the cytochrome-b5 reductase gene in an Indian patient: the molecular basis of type I methemoglobinemia.

نویسندگان

  • Roberto H Nussenzveig
  • H Bindu Lingam
  • Amos Gaikwad
  • Qiqing Zhu
  • Naijie Jing
  • Josef T Prchal
چکیده

We report here a novel mutation in the cytochrome b5 reductase gene resulting in type I methemoglobinemia. A single T->C transition in exon 8 at position 25985 was identified, changing codon 217 from Leu to Pro (L217P). The mutation is located in the NADH binding domain at the base of alpha-helix Nalpha3, a region of sequence highly conserved from yeast to man. A quantitative assessment of the thermodynamic cost of this mutation at 37 degrees C revealed a ten-fold drop in the free energy of stability. Alterations in hydrogen bonding and solvent accessibility surrounding residue 217 were predicted based on computer modeling.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

A novel nine base deletion mutation in NADH-cytochrome b5 reductase gene in an Indian family with recessive congenital methemoglobinemia-type-II

Recessive hereditary methemoglobinemia (RCM) associated with severe neurological abnormalities is a very rare disorder caused by NADH- cytochrome b5 reductase (cb5r) deficiency (Type II). We report a case of 11 month old male child who had severe mental retardation, microcephaly and gross global developmental delay with methemoglobin level of 61.1%. The diagnosis of NADH-CYB5R3 deficiency was m...

متن کامل

Serine-proline replacement at residue 127 of NADH-cytochrome b5 reductase causes hereditary methemoglobinemia, generalized type.

Hereditary methemoglobinemia is an autosomal recessive disorder characterized by NADH-cytochrome b5 reductase (b5R) deficiency. In an attempt to clarify the molecular mechanisms involved in the enzyme deficiency, we isolated the b5R gene from a patient homozygous for hereditary methemoglobinemia, generalized type, and compared its nucleotide sequence with that of the normal NADH-cytochrome b5R ...

متن کامل

Serine - Proline Replacement at Residue 127 of NADH - Cytochrome b 5 Reductase Causes Hereditary Methemoglobinemia

Hereditary methemoglobinemia is an autosomal recessive disorder characterized by NADH-cytochrome b5 reductase (b5R) deficiency. In an attempt to clarify the molecular mechanisms involved in the enzyme deficiency, we isolated the b5R gene from a patient homozygous for hereditary methemoglobinemia, generalized type, and compared its nucleotide sequence with that of the normal NADHcytochrome b5R g...

متن کامل

Clinical spectrum and molecular basis of recessive congenital methemoglobinemia in India.

We report the clinical features and molecular characterization of 23 patients with cyanosis due to NADH-cytochrome b5 reductase (NADH-CYB5R) deficiency from India. The patients with type I recessive congenital methemoglobinemia (RCM) presented with mild to severe cyanosis only whereas patients with type II RCM had cyanosis associated with severe neurological impairment. Thirteen mutations were ...

متن کامل

A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia.

Recessive congenital methemoglobinemia due to nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase (b5R) deficiency is classified into 2 clinical types: type 1 (erythrocyte type) and type 2 (generalized type). We found a Chinese family with type 1 recessive congenital methemoglobinemia, the patients from which were diagnosed according to clinical symptoms and b5R enzyme activity in ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Haematologica

دوره 91 11  شماره 

صفحات  -

تاریخ انتشار 2006