Mutations in HADHB, which encodes the β‐subunit of mitochondrial trifunctional protein, cause infantile onset hypoparathyroidism and peripheral polyneuropathy. Issue 5 (24th March 2014)

• Record Type: Journal Article
• Authors: Naiki, Misako; Ochi, Nobuhiko; Kato, Yusuke S.; Purevsuren, Jamiyan; Yamada, Kenichiro; Kimura, Reiko; Fukushi, Daisuke; Hara, Shinya; Yamada, Yasukazu; Kumagai, Toshiyuki; Yamaguchi, Seiji; Wakamatsu, Nobuaki
• Is Part Of: American journal of medical genetics. Volume 164:Issue 5(2014.)
• Page Start: 1180
• Page End: 1187
• Publication Date: 2014-03-24
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36434
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36434-sec-0001" sec-type="section"> <p>Mitochondrial trifunctional protein (MTP) is a hetero‐octamer composed of four α‐ and four β‐subunits that catalyzes the final three steps of mitochondrial β‐oxidation of long chain fatty acids. <italic>HADHA</italic> and <italic>HADHB</italic> encode the α‐subunit and the β‐subunit of MTP, respectively. To date, only two cases with MTP deficiency have been reported to be associated with hypoparathyroidism and peripheral polyneuropathy. Here, we report on two siblings with autosomal recessive infantile onset hypoparathyroidism, peripheral polyneuropathy, and rhabdomyolysis. Sequence analysis of <italic>HADHA</italic> and <italic>HADHB</italic> in both siblings shows that they were homozygous for a mutation in exon 14 of <italic>HADHB</italic> (c.1175C>T, [p.A392V]) and the parents were heterozygous for the mutation. Biochemical analysis revealed that the patients had MTP deficiency. Structural analysis indicated that the A392V mutation identified in this study and the N389D mutation previously reported to be associated with hypoparathyroidism are both located near the active site of MTP and affect the conformation of the β‐subunit. Thus, the present patients are the second and third cases of MTP deficiency associated with missense <italic>HADHB</italic> mutation and infantile onset hypoparathyroidism. Since MTP deficiency is a treatable disease, MTP deficiency should be considered when patients have hypoparathyroidism as the initial presenting feature in infancy. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>